Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Sitagliptin/metformin · 40 trials · 2 indications
Hemoglobin A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. The change from baseline represents the Week 20 A1C value minus the Week 0 (baseline) A1C value.
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 30 A1C minus the Week 0 A1C.
Documented symptomatic hypoglycemia is defined as an event during which typical symptoms of hypoglycemia are accompanied by a measured (e.g., by fingerstick) plasma glucose concentration ≤70 mg/dL (≤3.9 mmol/L). The event rate was the total number of events divided by follow-up time (participant-years), including multiple events from the same participant.
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
HbA1c is measured as percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent. Statistical analysis based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, time, prior use of AHAs, the interactions of treatment by time, time by prior use of AHAs, and treatment by time by prior use of AHAs with the constraint that the mean baseline is the same for both treatment groups.
A1C is blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Thus, this change from baseline reflects the Week 24 A1C minus the Week 0 A1C.
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product. The AE does not have to have a causal relationship with this treatment. The AE can include any unfavourable and unintended sign, symptom, or disease or any worsening (change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the pharmaceutical product.
Change from baseline in FPG at Week 6 based on longitudinal data analysis (LDA) model including both baseline and post-baseline measurements as response variable and term time.
An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.
Participants who were discontinued from study drug due to an adverse event during the 6 weeks of treatment.
An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.
A1C was measured as a percent. This change from baseline reflects the A1C percent at Week 24 minus the A1C percent at Week 0.
An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of pre-existing conditions.
Based on a constrained longitudinal data analysis (cLDA) model with terms for treatment, other prior antihyperglycemic agent (AHA) therapy status other than sitagliptin (yes/no), study drug regimen (just before meal/after meal), sitagliptin dosage (50 mg/100 mg), time and the interaction of time by treatment, time by other prior AHA therapy status, time by study drug regimen, time by sitagliptin dosage and study drug regimen by sitagliptin dosage, with a constraint that the mean baseline is the same for all treatment groups.
Change in daily insulin dose following 24 weeks of therapy (i.e., daily insulin dose at Week 24 minus daily insulin dose at baseline)
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline at Week 20 was estimated from a longitudinal data analysis model.
The number of participants experiencing ≥1 adverse event during Weeks 0-20 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
The number of participants who discontinued from study drug due to an adverse event during Weeks 0-20 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
The number of participants experiencing ≥1 adverse event during Weeks 0-56 were reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
The number of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent. Efficacy analyses treated data as missing after the initiation of rescue therapy.
Participant whole blood samples were collected at baseline and Week 30 to determine the LS mean HbA1c change from baseline. HbA1c is a measure of the percentage of glycated hemoglobin in the blood and provides an indication of participant blood glucose control in the 2 to 3 months prior to the evaluation.
Symptomatic hypoglycemia was defined as an episode with clinical symptoms attributed to hypoglycemia, without regard to glucose level. Participants were instructed to complete the Hypoglycemia Assessment Log (HAL) for any symptomatic episodes he or she believed represent hypoglycemia. If a fingerstick glucose was obtained before or shortly (i.e., within a few minutes) after treating, the value was recorded in the HAL. In addition, participants were instructed to record in the HAL any fingerstick glucose values ≤70 mg/dL (≤3.9 mmol/L) regardless of the presence of clinical symptoms.
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of the treatment administered.
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of the treatment administered.
Symptomatic hypoglycemic events were based on the participants own self-reported symptoms (for example, but not limited to the following: faintness, headache, confusion, anxiety, sweating, tremor, palpitations, nausea, pallor, dizziness, hunger, sudden behavioral change).
Change from baseline reflects the Week 24 value minus the baseline value. A1C represents the percentage of glycosylated hemoglobin.
Safety \& tolerability were measured in terms of the # of participants with \>=1 adverse event (AE), \>=1 drug-related AE, \>=1 serious AE (SAE), or discontinued treatment due to an AE. SAEs included events occurring after initiation of glycemic rescue therapy. AE is defined as any unfavorable/unintended change in structure, function, or chemistry of the body temporally associated with the use of SPONSOR's product. SAE is defined as any AE that results in death, is life-threatening, an overdose, causes or prolongs in-patient hospitalization, or considered medically significant by the investigator.
Change from baseline reflects the Week 26 value minus the baseline value. A1C represents the percentage of glycosylated hemoglobin.
Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.
Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.
A1C represents the percentage of glycosylated hemoglobin.
The change in A1C, compared to baseline for the Sita/Met FDC and the pioglitazone groups at Week 40. A1C represents percentage of glycosylated hemoglobin.
The change in A1C compared to baseline was measured for the participants treated with sitagliptin or pioglitazone at Week 12. Sitagliptin was the only intervention administered to the Sita/Met FDC group during this phase. A1c represents percentage of glycosylated hemoglobin.
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent.
Change from the baseline measurement, where the baseline measurement was obtained at randomization (0 week) before receiving study medication.
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 18 HbA1c percent minus the Week 0 HbA1c percent.
A1C is measured as percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent. The study hypothesis comparison was between sitagliptin versus placebo.
Change from baseline at Week 24 is defined as Week 24 minus Week 0.
A1C was measured as a percent. Thus, this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent.
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the Week 0 HbA1c percent.
The Swallowing Ability Questionnaire was completed on Day 2 after the participant received two matching placebo tablets (excluding marking) following consumption of a low- to moderate-fat meal in pediatric participants aged 10 to 17 years. The questionnaire consisted of five parts: could only swallow study med with help, easy to start swallowing study med, easy to swallow study med, felt like study med got stuck in throat, and had to swallow study med more than once. The number of participants who strongly agreed or agreed in each of the five parts is reported.
The Swallowing Ability Questionnaire was completed on Day 4 after the participant received two matching placebo tablets (excluding marking) following consumption of a low- to moderate-fat meal in pediatric participants aged 10 to 17 years. The questionnaire consisted of five parts: could only swallow study med with help, easy to start swallowing study med, easy to swallow study med, felt like study med got stuck in throat, and had to swallow study med more than once. The number of participants who strongly agreed or agreed in each of the five parts is reported.
The Swallowing Ability Questionnaire was completed on Day 6 after the participant received two matching placebo tablets (excluding marking) following consumption of a low- to moderate-fat meal in pediatric participants aged 10 to 17 years. The questionnaire consisted of five parts: could only swallow study med with help, easy to start swallowing study med, easy to swallow study med, felt like study med got stuck in throat, and had to swallow study med more than once. The number of participants who strongly agreed or agreed in each of the five parts is reported.
The Swallowing Ability Questionnaire was completed on Day 9 after the participant received two matching placebo tablets (excluding marking) following consumption of a low- to moderate-fat meal in pediatric participants aged 10 to 17 years. The questionnaire consisted of five parts: could only swallow study med with help, easy to start swallowing study med, easy to swallow study med, felt like study med got stuck in throat, and had to swallow study med more than once. The number of participants who strongly agreed or agreed in each of the five parts is reported.
In this study, metformin products were withheld 24 hours (hrs) prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hrs post study drug administration. Owing to resumption of therapeutic metformin administration 24 hrs after sitagliptin/metformin XR administration for all participants, metformin pharmacokinetic analyses were restricted to maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax) and area under the curve 0 to 24 hrs (AUC0-24hr). Therefore, metformin arm is not included in this endpoint.
Due different units of measure for sitagliptin and metformin, metformin data are presented in another endpoint.
In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration. Due different units of measure for sitagliptin and metformin, sitagliptin data are presented in another endpoint.
In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration. Owing to resumption of therapeutic metformin administration 24 hours after sitagliptin/metformin XR administration for all participants, metformin pharmacokinetic analyses were restricted to Cmax, Tmax and AUC0-24hr. Therefore, metformin arm is not included in this endpoint.
Due different units of measure for sitagliptin and metformin, metformin data are presented in another endpoint.
In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration. Due different units of measure for sitagliptin and metformin, sitagliptin data are presented in another endpoint.
In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration.
In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration. Owing to resumption of therapeutic metformin administration 24 hours after sitagliptin/metformin XR administration for all participants, metformin pharmacokinetic analyses were restricted to Cmax, Tmax and AUC0-24hr. Therefore, metformin arm is not included in this endpoint.
An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Vital sign measurements included blood pressure, heart rate, respiratory rate, and oral temperature.
An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
Percent inhibition of DPP-4 activity at 24 hours after the Day 5 morning dose (i.e., at trough) was determined by analysis of blood samples collected from the study participants.
AUC (0-t) is the area under the curve for the plot showing plasma concentration against time from time zero to the time of the last quantifiable concentration for sitagliptin 50 mg, metformin 500 mg and metformin 850 mg.
Cmax is the peak serum concentration of a therapeutic drug after administration; and is used to determine the rate and extent of drug absorption. Cmax is reported for sitagliptin 50 mg, metformin 500 mg and metformin 850 mg.
ISR was estimated by the deconvolution of peripheral C-peptide concentrations using a 2-compartment model that utilizes population C-peptide kinetic parameters.
Meal was given 2 hours postdose. Blood samples for determination of active GLP-1 concentration were collected (4 hours postmeal) on Day 2 in each treatment period.
Serum samples were used to determine the AUC from time 0 to infinity for sitagliptin. The placebo group is not included in the table below; this outcome measure only evaluated the sitagliptin groups.
Serum samples were used to determine the AUC from time 0 to infinity for metformin.
The 24-hour WMG was calculated as the area under the 24-hour glucose curve (AUC(0-24 hr)) divided by 24 using linear trapezoidal method.
| Arm | Type | Description |
|---|---|---|
| Sitagliptin first, then Placebo | EXPERIMENTAL | Sitagliptin 100 mg/d for 6 weeks Wash-out 14 days Placebo for 6 weeks |
| Placebo first, then Sitagliptin | PLACEBO_COMPARATOR | Placebo for 6 weeks Wash-out 14 days Sitagliptin 100 mg/d for 6 weeks |
| Sitagliptin | EXPERIMENTAL | Participants will receive sitagliptin 100 mg once daily for 20 weeks. They will also receive immediate-release metformin (Met-IR), which will be titrated from a baseline dose of 1000 mg/day (500 mg/twice a day \[b.i.d.\]) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants will also receive glycemic rescue therapy as needed. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo matching sitagliptin once daily for 20 weeks. They will also receive Met-IR, which will be titrated from baseline dose of 1000 mg/day (500 mg/b.i.d.) up to 2000 mg/day (1000 mg/b.i.d.) by Day 15. Participants will also receive glycemic rescue therapy as needed. |
| Sitagliptin + Ipragliflozin | EXPERIMENTAL | Sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise. |
| Placebo + Ipragliflozin | ACTIVE_COMPARATOR | Placebo to sitagliptin, oral, once daily for 24 weeks plus ipragliflozin (base therapy), in addition to diet and exercise. |
| Dapagliflozin | ACTIVE_COMPARATOR | Participants receive dapagliflozin 5 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 4 weeks followed by dapagliflozin 10 mg once daily plus matching placebo for sitagliptin 100 mg once daily for 20 weeks. Participants continue pre-study metformin (at least 1500 mg daily) alone or in combination with a sulfonylurea agent (at a dose of ≥ 50% maximum labeled dose in the country of the investigational site) throughout the duration of the study. |
| Sitagliptin 100 mg/simvastatin 40 mg FDC | EXPERIMENTAL | Sitagliptin 100 mg/simvastatin 40 mg FDC once daily in the evening for 6 weeks. Participants will continue pre-study dose of metformin \>=1000 mg per day. |
| Metformin 500 mg q.d. | EXPERIMENTAL | Participants will receive sitagliptin daily (continuing their pre-study dose), 2 metformin 250 mg tablets in the morning and 1 matching placebo tablet in the evening. |
| Metformin 250 mg b.i.d. | EXPERIMENTAL | Participants will receive sitagliptin daily (continuing their pre-study dose), 1 metformin 250 mg tablet and 1 matching placebo tablet in the morning and 1 metformin 250 mg tablet in the evening. |
| Sitagliptin/Metformin | EXPERIMENTAL | Participants received one tablet of sitagliptin/metformin and one tablet of metformin-placebo, administered twice daily prior to the morning and evening meals, for up to 20 weeks in the base study alone, or for up to 54 weeks if the participant also entered the extension study. Participants in this arm were enrolled in protocol MK-0431A-170. |
| Metformin | PLACEBO_COMPARATOR | Participants received one tablet of metformin and one tablet of placebo to sitagliptin/metformin, administered twice daily prior to the morning and evening meals, for up to 20 weeks in the base study alone, or for up to 54 weeks if the participant also entered the extension study. Participants in this arm were enrolled in protocol MK-0431A-170. |
| Sitagliptin/Metformin XR | EXPERIMENTAL | Participants received two tablets of sitagliptin/metformin XR and two tablets of metformin XR placebo, administered once daily with a meal, for up to 54 weeks. Participants in this arm were enrolled in protocol MK-0431A-289. |
| Metformin XR | PLACEBO_COMPARATOR | Participants received two tablets of metformin XR and two tablets of placebo to sitagliptin/metformin XR, administered once daily with a meal, for up to 54 weeks. Participants in this arm were enrolled in protocol MK-0431A-289. |
| Sitagliptin 50 mg + metformin 500 mg | EXPERIMENTAL | Sitagliptin 50 mg and metformin 500 mg twice a day for 24 weeks. |
| Sitagliptin 50 mg + metformin 850 mg | EXPERIMENTAL | Sitagliptin 50 mg and metformin 850 mg twice a day for 24 weeks. |
| Metformin 500 mg | ACTIVE_COMPARATOR | Metformin 500 mg twice daily for 24 weeks. |
| Metformin 850 mg | ACTIVE_COMPARATOR | Metformin 850 mg twice daily for 24 weeks. |
| Sitagliptin 100 mg | EXPERIMENTAL | Sitagliptin 100 mg once daily for 24 weeks. |
| Glimepiride | ACTIVE_COMPARATOR | Glimepiride 1-6 mg QD |
| Sulfonylurea Therapy | ACTIVE_COMPARATOR | Usual sulfonylurea therapy with or without metformin |
| placebo/pioglitazone | ACTIVE_COMPARATOR | Phase A (Weeks 0-24): placebo to Sitagliptin 100 mg; Phase B (Weeks 24-54): placebo to Sitagliptin 100 mg + pioglitazone 30 mg |
| Pioglitazone 15 mg | EXPERIMENTAL | - |
| Pioglitazone 30 mg | EXPERIMENTAL | - |
| Pioglitazone 45 mg | EXPERIMENTAL | - |
| Sitagliptin 100 mg/ Pioglitazone 15 mg | EXPERIMENTAL | - |
| Sitagliptin 100 mg/ Pioglitazone 30 mg | EXPERIMENTAL | - |
| Sitagliptin 100 mg/ Pioglitazone 45 mg | EXPERIMENTAL | - |
| Sita/Met FDC | EXPERIMENTAL | In Phase A (Treatment Day 1 to Week 12), participants were administered 100 mg once daily (q.d.) of sitagliptin and matching placebo to 15 mg pioglitazone q.d. for 6 weeks followed by matching placebo to 30 mg pioglitazone for the next 6 weeks. In Phase B (Treatment Week 12-Week 40), participants were switched to the Sita/Met Fixed-Dose Combination (FDC) at a dose of 50/500 mg twice a day (b.i.d.), which was increased to 50/1000 mg b.i.d. over a period of 4 weeks; as well as matching placebo to 45 mg pioglitazone. |
| Pioglitazone | ACTIVE_COMPARATOR | In Phase A (Treatment Day 1 up to Week 12), randomized participants in the pioglitazone group were administered 15 mg q.d. of pioglitazone and matching placebo to sitagliptin. At Week 6, participants were up-titrated to 30 mg pioglitazone q.d. In Phase B (Treatment Week 12 to Week 40), participants were administered 45 mg pioglitazone q.d.; as well as matching placebo to Sita/Met FDC (50/500 increased to 50/1000 b.i.d. after 4 weeks). |
| 1 | EXPERIMENTAL | Drug |
| 2 | ACTIVE_COMPARATOR | Active comparator |
| Rosiglitazone | ACTIVE_COMPARATOR | rosiglitazone 8 mg |
| 3 | EXPERIMENTAL | 50 mg QD 12-week |
| 4 | EXPERIMENTAL | 100 mg QD 12-week |
| 5 | EXPERIMENTAL | 200 mg QD 12-week |
| Sitagliptin/metformin XR followed by placebo | EXPERIMENTAL | Day 1 (Period 1): participants will receive a single dose of two sitagliptin/metformin XR tablets with a low- to moderate-fat meal (breakfast). Days 2-4 (Period 1): participants will receive a single dose of two matching placebo tablets. Days 5-9 (Period 2): participants will receive a single dose of two matching placebo tablets with the evening meal. |
| Placebo only | PLACEBO_COMPARATOR | Days 1-4 (Period 1): participants will receive a single dose of two matching placebo tablets. Days 5-9 (Period 2): participants will receive a single dose of two matching placebo tablets with the evening meal. |
| Treatment Sequence 1 | EXPERIMENTAL | Sitagliptin 100 mg in Period 1 followed by saxagliptin 5 mg in Period 2 followed by vildagliptin 50 mg BID in Period 3 followed by placebo in Period 4 followed by vildagliptin 50 mg in Period 5 |
| Treatment Sequence 2 | EXPERIMENTAL | Saxagliptin 5 mg in Period 1 followed by vildagliptin 50 mg in Period 2 followed by placebo in Period 3 followed by sitagliptin 100 mg in Period 4 followed by vildagliptin 50 mg BID in Period 5 |
| Treatment Sequence 3 | EXPERIMENTAL | Vildagliptin 50 mg in Period 1 followed by vildagliptin 50 mg BID in Period 2 followed by sitagliptin 100 mg in Period 3 followed by saxagliptin 5 mg in Period 4 followed by placebo in Period 5 |
| Treatment Sequence 4 | EXPERIMENTAL | Vildagliptin 50 mg BID in Period 1 followed by placebo in Period 2 followed by saxagliptin 5 mg in Period 3 followed by vildagliptin 50 mg in Period 4 followed by sitagliptin 100 mg in Period 5 |
| Treatment Sequence 5 | EXPERIMENTAL | Placebo in Period 1 followed by sitagliptin 100 mg in Period 2 followed by vildagliptin 50 mg in Period 3 followed by vildagliptin 50 mg BID in Period 4 followed by saxagliptin 5 mg in Period 5 |
| Treatment Sequence 6 | EXPERIMENTAL | Sitagliptin 100 mg in Period 1 followed by vildagliptin 50 mg in Period 2 followed by saxagliptin 5 mg in Period 3 followed by placebo in Period 4 followed by vildagliptin 50 mg BID in Period 5 |
| Treatment Sequence 7 | EXPERIMENTAL | Saxagliptin 5 mg in Period 1 followed by vildagliptin 50 mg BID in Period 2 followed by vildagliptin 50 mg in Period 3 followed by sitagliptin 100 mg in Period 4 followed by placebo in Period 5 |
| Treatment Sequence 8 | EXPERIMENTAL | Vildagliptin 50 mg in Period 1 followed by placebo in Period 2 followed by vildagliptin 50 mg BID in Period 3 followed by saxagliptin 5 mg in Period 4 followed by sitagliptin 100 mg in Period 5 |
| Treatment Sequence 9 | EXPERIMENTAL | Vildagliptin 50 mg BID in Period 1 followed by sitagliptin 100 mg in Period 2 followed by placebo in Period 3 followed by vildagliptin 50 mg in Period 4 followed by saxagliptin 5 mg in Period 5 |
| Treatment Sequence 10 | EXPERIMENTAL | Placebo in Period 1 followed by saxagliptin 5 mg in Period 2 followed by sitagliptin 100 mg in Period 3 followed by vildagliptin 50 mg BID in Period 4 followed by vildagliptin 50 mg in Period 5 |
| 1. Sit + Met500 / SitMet500 FDC / SitMet850 FDC / Sit + Met850 | EXPERIMENTAL | Participants were administered treatment in the following sequence with a minimum 7 day washout period between treatments: * Co-administration of 50 mg sitagliptin and 500 mg metformin * sitagliptin/metformin 50 mg/500 mg FDC tablet * sitagliptin/metformin 50 mg/850 mg FDC tablet * Co-administration of 50 mg sitagliptin and 850 mg metformin |
| 2. SitMet500 FDC / Sit + Met850 / Sit + Met500 / SitMet850 FDC | EXPERIMENTAL | Participants were administered treatment in the following sequence with a minimum 7 day washout period between treatments: * sitagliptin/metformin 50 mg/500 mg FDC tablet * Co-administration of 50 mg sitagliptin and 850 mg metformin * Co-administration of 50 mg sitagliptin and 500mg metformin * sitagliptin/metformin 50 mg/850 mg FDC tablet |
| 3. Sit + Met850 / SitMet850 FDC / SitMet500 FDC / Sit + Met500 | EXPERIMENTAL | Participants were administered treatment in the following sequence with a minimum 7 day washout period between treatments: * Co-administration of 50 mg sitagliptin and 850 mg metformin * sitagliptin/metformin 50 mg/850 mg FDC tablet * sitagliptin/metformin 50 mg/500 mg FDC tablet * Co-administration of 50 mg sitagliptin and 500mg metformin |
| 4. SitMet850 FDC / Sit + Met500 / Sit + Met850 / SitMet500 FDC | EXPERIMENTAL | Participants were administered treatment in the following sequence with a minimum 7 day washout period between treatments: * sitagliptin/metformin 50 mg/850 mg FDC tablet * Co-administration of 50 mg sitagliptin and 500 mg metformin * Co-administration of 50 mg sitagliptin and 850 mg metformin * sitagliptin/metformin 50 mg/500 mg FDC tablet |
| Sitagliptin/Sitagliptin/Placebo | EXPERIMENTAL | Sitagliptin in 2 of 3 treatment periods and Placebo in 1 of 3 treatment periods |
| Sitagliptin/Placebo/Sitaglipitin | EXPERIMENTAL | Sitagliptin in 2 of 3 treatment periods and Placebo in 1 of 3 treatment periods |
| Placebo/Sitagliptin/Sitagliptin | EXPERIMENTAL | Sitagliptin in 2 of 3 treatment periods and Placebo in 1 of 3 treatment periods |
| Sitagliptin + placebo metformin | EXPERIMENTAL | - |
| Metformin + placebo sitagliptin | EXPERIMENTAL | - |
| Sitagliptin + metformin | EXPERIMENTAL | Co-administration of sitagliptin and metformin |
| Placebo sitagliptin + placebo metformin | PLACEBO_COMPARATOR | Co-administration of placebo to sitagliptin and placebo to metformin |
| Sitagliptin 50 mg | EXPERIMENTAL | Participants were randomized to sitagliptin 50 mg |
| Sitagliptin 200 mg | EXPERIMENTAL | Participants were randomized to a single dose of sitagliptin 200 mg |
| Placebo to sitagliptin | PLACEBO_COMPARATOR | Participants were randomized to matching placebo to sitagliptin 50 mg, 100 mg, or 200 mg |
| Sita + Met then Sita/Met FDC | ACTIVE_COMPARATOR | Participants receive sitagliptin (Sita) 50 mg and metformin (Met) 500 mg individual tablets administered concomitantly as a single dose during Period 1 followed by a 7-day washout followed by sitagliptin/metformin (Sita/Met) 50/500 mg FDC tablet administered as a single dose during Period 2. |
| Sita/Met FDC then Sita + Met | ACTIVE_COMPARATOR | Participants receive sitagliptin/Metformin 50 mg/500 mg FDC tablet administered as a single dose during Period 1 followed by a 7-day washout followed by sitagliptin 50 mg and metformin 500 mg individual tablets administered concomitantly as a single dose during Period 2. |
| A | ACTIVE_COMPARATOR | Sitagliptin alone |
| B | ACTIVE_COMPARATOR | Metformin alone |
| C | EXPERIMENTAL | Sitagliptin and metformin concomitantly |
| D | PLACEBO_COMPARATOR | Placebo |
| Name | Type | Description |
|---|---|---|
| Sitagliptin | DRUG | Sitagliptin 100 mg/d for 6 weeks |
| Placebo | DRUG | Placebo for 6 weeks |
| Metformin IR | DRUG | All participants will take Met-IR as background medication. Initially, they will take 1 x 500 mg tablet Met-IR b.i.d. (1000 mg/day). After randomization, all participants will be titrated to 2 x 500 mg tablets of Met-IR b.i.d. (2000 mg/day). |
| Placebo to sitagliptin | DRUG | Placebo to sitagliptin, 100 mg, oral, once daily for 30 weeks |
| Metformin | DRUG | At least 1500 mg/day, oral, twice daily for participants entering the study on immediate-release metformin + sitagliptin or a fixed dose combination (FDC). |
| Metformin XR | DRUG | At least 1500 mg/day, oral, once daily for participants entering the study on extended-release metformin + sitagliptin or a FDC. |
| Insulin glargine | DRUG | Insulin glargine (LANTUS®) initiated at 10 units and titrated based on a treat-to-target algorithm to achieve fasting glucose levels of 72-100 mg/dL (4-5.6 mmol/L); administered once daily subcutaneously. |
| Ipragliflozin | DRUG | 50 mg tablet administered orally as background medication |
| Dapagliflozin | DRUG | Dapagliflozin 5 mg or 10 mg oral capsule. Up-titration to dapagliflozin 10 mg daily may be delayed if participant is unable to tolerate up-titration in the opinion of the investigator. Dapagliflozin 10 mg daily may be down-titrated to dapagliflozin 5 mg daily if participant is unable to tolerate the higher dose in the opinion of the investigator. |
| Matching placebo to sitagliptin | DRUG | Matching placebo to sitagliptin 100 mg oral tablet |
| Matching placebo to dapagliflozin | DRUG | Matching placebo to dapagliflozin 5 mg or 10 mg oral capsule. Up-titration to matching placebo to dapagliflozin 10 mg daily may be delayed if participant is unable to tolerate up-titration in the opinion of the investigator. Matching placebo to dapagliflozin 10 mg daily may be down-titrated to matching placebo to dapagliflozin 5 mg daily if participant is unable to tolerate the higher dose in the opinion of the investigator. |
| Sulfonylurea | DRUG | This medication is a standard-of-care medication and is administered in an open-label fashion. The dose of the sulfonylurea agent will be required to be at least 50% of maximum labeled dose, consistent with near maximum efficacy of the sulfonylurea agent. |
| Sitagliptin 100 mg/simvastatin 40 mg FDC | DRUG | Sitagliptin 100 mg/simvastatin 40 mg FDC tablet administered once daily in the evening for 6 weeks |
| Insulin | BIOLOGICAL | Participants can be on on pre-mixed (mixture of rapid- and long-acting insulin) or intermediate- or long-acting insulin at a dose of at least 12 U/day. |
| Gliclazide | DRUG | Participants will continue ongoing open-label therapy with gliclazide (dosed according to the China drug label) throughout the study. |
| Glimepiride | DRUG | Participants will continue ongoing open-label therapy with glimepiride (dosed according to the China drug label) throughout the study. |
| Comparator: Placebo | DRUG | Placebo to sitagliptin once daily for 24 weeks |
| Sitagliptin plus metformin | DRUG | Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1700 mg or 2000 mg of metformin. Dosage of metformin was based on each participant's daily metformin dose prior to enrollment. |
| Placebo to metformin | DRUG | Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to metformin. |
| Placebo to sitagliptin plus metformin | DRUG | Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to sitagliptin plus metformin. |
| Sitagliptin plus metformin XR | DRUG | Participants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1500 mg or 2000 mg of metformin. Dosage of metformin XR was based on each participant's daily metformin dose prior to enrollment. |
| Placebo to metformin XR | DRUG | Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to metformin XR. |
| Placebo to sitagliptin plus metformin XR | DRUG | Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to sitagliptin plus metformin XR. |
| Sitagliptin phosphate | DRUG | Sitagliptin, 100 mg tablet once daily, orally for 24 weeks |
| Acarbose | DRUG | Acarbose 50 mg or 100 mg tablet, 3 times daily, orally (continuing on the stable dose established prior to screening) for 24 weeks |
| Sitagliptin 50 mg | DRUG | Sitagliptin 50 mg tablet twice a day, prior to the morning and evening meal, for 24 weeks. |
| Metformin 500 mg | DRUG | Metformin 500 mg tablet twice daily, prior to the morning and evening meal, for 24 weeks. |
| Sitagliptin 100 mg | DRUG | Sitagliptin 100 mg once daily for 24 weeks. |
| Metformin 850 mg | DRUG | Metformin 850 mg tablet twice daily, prior to the morning and evening meal, for 24 weeks. |
| Placebo to Glimepiride | DRUG | Matching placebo tablets to glimepiride to allow for blinding. |
| Comparator: placebo to pioglitazone | DRUG | Phase B (Weeks 24-54): placebo to pioglitazone 30 mg once a day for 30 weeks |
| Comparator: placebo to Sitagliptin | DRUG | Phase A (Weeks 0-24): placebo to Sitagliptin 100 mg once a day for 24 weeks; Phase B (Weeks 24-54): placebo to Sitagliptin once a day for 30 weeks |
| Comparator: pioglitazone | DRUG | Phase B (Weeks 24-54): pioglitazone 30 mg once a day for 30 weeks |
| Glimepiride or gliclazide | DRUG | Phase A (Weeks 0-24): stable dose, as prescribed by investigator, of glimepiride or gliclazide; Phase B (Weeks 24-54): stable dose, as prescribed by investigator, of glimepiride or gliclazide |
| Pioglitazone rescue therapy | DRUG | Phase A (Weeks 0-24): participants not meeting specific glycemic goals will receive pioglitazone (open label) at a dose determined by the investigator. These participants will not initiate Phase B (Weeks 24-54) double blind pioglitazone. |
| Pioglitazone | DRUG | Participants taking 30 mg or more pioglitazone oral tablet(s) daily at screening in combination with metformin will enter a 4-week dose-stable period followed by a 2-week single-blind run-in and a 26-week treatment period. Participants taking 4 mg or more rosiglitazone oral tablet(s) daily at screening in combination with metformin were to be switched to a corresponding dose of pioglitazone prior to starting a 4-week dose-stable period. Participants who are taking less than 30 mg/day or no pioglitazone at screening will be titrated to a stable dose of at least 30 mg pioglitazone once daily over a maximum of 4 weeks followed by a dose-stable period of 10 weeks, a 2-week single-blind placebo run-in, and a 26-week treatment period. Total treatment with pioglitazone will be up to 42 weeks. |
| Glipizide | DRUG | Participants not meeting specific glycemic controls during the 26-week treatment period will use glipizide oral tablets as rescue therapy. In countries where glipizide is not available, participants will receive a sulfonylurea marketed in that country. |
| Comparator: Sitagliptin phosphate | DRUG | All participants will receive placebo tablets two weeks prior to treatment period. Participants will receive sitagliptin phosphate 100 mg tablets once daily (q.d.) and continue on stable dose of metformin therapy (500 or 850 mg twice daily). Treatment period of 24 weeks. |
| Pioglitazone hydrochloride | DRUG | Pioglitazone 15 mg, 30 mg, or 45 mg tablets or capsules (blinded) orally once daily for 54 weeks. Participants randomized to receive pioglitazone 45 mg as monotherapy or in combination with sitagliptin were to start on pioglitazone 30 mg at Week 1 and undergo uptitration to pioglitazone 45 mg at Week 4. |
| Matching placebo to pioglitazone | DRUG | Matching placebo to pioglitazone tablets or capsules orally once daily for 54 weeks. |
| Comparator: sitagliptin phosphate (sitagliptin) | DRUG | sitagliptin 100 mg tablet q.d. orally for a 12-wk treatment period |
| sitagliptin phosphate (+) metformin hydrochloride | DRUG | sitagliptin/metformin HCl (Sita/Met) 50/500 mg b.i.d. orally and then 50/1000 mg b.i.d. orally for a 28-wk treatment period |
| Matching Placebo to Sita/Met FDC | DRUG | matching placebo to Sita/Met FDC - 50/500 mg b.i.d. for 4 weeks and then 50/1000 mg b.i.d. orally for a 28-wk treatment period (Week 12 to Week 40). |
| Comparator: metformin hydrochloride | DRUG | (4) Metformin 500mg tablets once daily (q.d.) for a 24-wk treatment period. |
| Comparator : placebo (unspecified) | DRUG | sitagliptin 100 mg Pbo tablet qd for a 24-wk treatment period. |
| Comparator: sitagliptin phosphate (MK0431) | DRUG | Sitagliptin (MK0431) 50 or 100 mg once daily for 40 weeks |
| Comparator: placebo (unspecified) | DRUG | Placebo once daily for 12 weeks |
| rosiglitazone | DRUG | Subjects taking 4mg or greater rosiglitazone at screening will enter a 6 week stable dose period followed by a 54 week treatment period. Subjects who are taking less than 4mg/day or no rosiglitazone at screening will be titrated to a stable dose of at least 4mg over a a maximum of 8 weeks followed by a dose stable period of up to 12 weeks then a 54 week treatment period. Total treatment will be up to 77 weeks. |
| Comparator: Rosiglitazone | DRUG | Rosiglitazone 8 mg administered as two 4 mg capsules once daily in the morning for up to 18 weeks. |
| Comparator: Metformin | DRUG | Open-label metformin was supplied by the Sponsor as 500, 850, or 1000 mg oral tablets administered at a daily dose of \>= 1500 mg. |
| Sitagliptin/metformin XR | DRUG | Fixed dose combination tablet of immediate-release sitagliptin 50 mg and extended-release (XR) metformin 1000 mg (total daily dose, sitagliptin 100 mg and metformin XR 2000 mg). |
| Thyroid hormone | DRUG | Concomitant use of thyroid hormone (eg, levothyroxine) is permitted during the study provided the participant has been receiving a stable dose for at least 12 weeks prior to study drug administration and is euthyroid as documented by thyroid stimulating hormone testing at prestudy. Administration of thyroid hormone will be withheld for 24 hours prior to study drug administration and for 24 hours postdose. |
| Saxagliptin 5 mg | DRUG | Saxagliptin 5 mg: one saxagliptin 5 mg tablet once daily in the morning following a fast of at least approximately 8 hours on Days 1 through 5 in one out of five treatment periods. |
| Vildagliptin 50 mg | DRUG | Vildagliptin 50 mg: one vildagliptin 50 mg tablet once daily in the morning following a fast of at least approximately 8 hours on Days 1 through 5 in one out of five treatment periods. |
| Vildagliptin 50 mg BID | DRUG | Vildagliptin 50 mg BID: one vildagliptin 50 mg tablet BID (twice daily), once in the morning following a fast of at least approximately 8 hours and once in the evening on Days 1 through 5 in one out of five treatment periods. |
| Co-administration of 50 mg sitagliptin and 500 mg metformin | DRUG | Co-administration of 50 mg sitagliptin and 500 mg China-sourced metformin as individual tablets with 240 ml water on Day 1 of the relevant treatment period (Sit + Met500) after fasting for at least 10 hours. |
| sitagliptin/metformin 50 mg/500 mg tablet | DRUG | Single dose administration of the final marketing image (FMI) sitagliptin/metformin 50 mg/500 mg fixed-dose combination (FDC) tablet with 240 ml water on Day 1 of the relevant treatment period (SitMet850 FDC) after fasting for at least 10 hours. |
| Co-administration of 50 mg sitagliptin and 850 mg metformin | DRUG | Co-administration of 50 mg sitagliptin and 850 mg China sourced metformin as individual tablets with 240 ml water on Day 1 of the relevant treatment period (Sit + Met850) after fasting for at least 10 hours. |
| sitagliptin/metformin 50 mg/850 mg tablet | DRUG | Single dose administration of the FMI sitagliptin/metformin 50 mg/850 mg FDC tablet with 240 ml water on Day 1 of the relevant treatment period (SitMet850 FDC) after fasting for at least 10 hours. |
| metformin hydrochloride | DRUG | Metformin 500 mg tablet in the morning and evening on Day 1 and two 500 mg tablets of metformin (total dose 1000 mg) on Day 2 in the morning. There will be a 7-day washout between treatment periods. |
| Comparator: placebo sitagliptin | DRUG | Placebo to sitagliptin 100 mg in the morning on Days 1 and 2. There will be a 7-day washout between treatment periods. |
| Comparator: placebo metformin | DRUG | Placebo to metformin 500 mg tablet in the morning and evening on Day 1 and two placebo to metformin 500 mg tablets (1000 mg total dose) in the morning of Day 2. There will be a 7-day wash out between treatment periods. |
| Comparator: matching placebo | DRUG | Participants will fast 8 hours prior to dosing. All doses will be given with 240 ml of water. Participants received either a single oral dose of matching placebo to sitagliptin 50 mg, 100 mg, or 200 mg. |
| Sitagliptin phosphate/metformin hydrochloride FDC | DRUG | Single dose sitagliptin/metformin 50/500 mg FDC tablet after consumption of a high-fat meal in one of two treatment periods. |
| Placebo tablet | DRUG | placebo PO (placebo control for sitagliptin) for three days |
| Sitagliptin tablet | DRUG | Sitagliptin 100 mg PO for three days. |
| Saline infusion | DRUG | Saline IV (placebo control for exendin(9-39)) on two consecutive study days |
| Exendin(9-39) infusion | DRUG | Exendin(9-39) IV on two consecutive study days. |
| Comparator: sitagliptin and metformin | DRUG | 100 mg sitagliptin once daily and 500 mg metformin twice daily on Day 1 and 100 mg sitagliptin once daily and 1000 mg metformin once daily on Day 2 in one of four treatment periods. |
Inclusion Criteria: * Males 18 to 65 years of age. * Post-menopausal women under age 65 on stable medical therapy for 6 months before the study (the patient should have demonstrated stable lipid panels) * Women should not be on hormone replacement therapy (no recent starting or stopping) * Type 2 d...
Sitagliptin is used for the treatment of Type 2 Diabetes Mellitus (T2DM), including Type 2 Diabetes, Diabetes Mellitus Type 2, and Type II Diabetes Mellitus. It is a small molecule being developed by Merck & Company, Inc. for the metabolic therapeutic area.
Sitagliptin is a small molecule developed for Type 2 Diabetes Mellitus. The specific molecular target is not disclosed in the available information. It is being studied in clinical trials for its effects on glucose metabolism in patients with Type 2 Diabetes.
Sitagliptin is developed by Merck & Company, Inc., which trades under the ticker symbol MRK. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with Type 2 Diabetes Mellitus.
Sitagliptin is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The drug is being studied in early-stage trials to assess its pharmacokinetics, safety, and tolerability in patients with Type 2 Diabetes.
Sitagliptin has been studied in several Phase 1 clinical trials, including NCT00541229, NCT00730275, NCT00975052, and NCT01093794. These trials evaluated dose comparison, pharmacokinetics in adolescents, effects on incretin hormones, and bioequivalence of a combination tablet, all in Type 2 Diabetes.
Sitagliptin is the generic name for the drug marketed as Januvia. The available information refers to the drug as sitagliptin, and it is being developed by Merck & Company, Inc. for the treatment of Type 2 Diabetes Mellitus.