Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Sitagliptin · 23 trials · 15 indications
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. Change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C.
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. The Placebo (pooled) arm was a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms for analysis purposes.
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline was estimated as the Week 20 A1C minus the Week 0 A1C from a longitudinal data analysis (LDA) model. The placebo arm in this comparison is a pooling of the Placebo/Metformin and Placebo/Sitagliptin arms. The Statistical Analysis Plan (SAP) did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.
The number of participants experiencing ≥1 adverse event during Weeks 0-56 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 was reported. An adverse event is any untoward medical occurrence in a person administered a pharmaceutical product and does not have to have a causal relationship with this treatment. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.
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.
The percentage of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is any untoward medical occurrence in a person administered a pharmaceutical product and does not have to have a causal relationship with this treatment. The SAP did not specify for the Metformin arm to be included in statistical comparisons, so results for this arm are provided separately.
A1C is measured as percent. Thus, this change from baseline reflects the Week 26 A1C percent minus the Week 0 A1C percent.
Change from baseline measurement, where the baseline measurement was obtained at randomization (Week 0) before receiving study medication. This study used Japan Diabetes Society (JDS)-certified HbA1c values, the standard at the time when the study was conducted (HbA1c \[National Glycohemoglobin Standardization Program; NGSP\] = HbA1c (JDS-HbA1c \[%\]) + 0.4%).
Patient-level HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 30 HbA1c percent minus the Week 0 HbA1c percent.
Change from baseline in mean hemoglobin A1c after treatment with sitagliptin for 54 weeks. Hemoglobin A1c is the percent of hemoglobin that is glycated. Results for the glipizide arm are not reported in this table because the primary outcome measure is for the sitagliptin arm only.
Reported experiences assessed by investigators as adverse events, excluding data after initiation of glycemic rescue therapy.
A1C represents percentage of glycosylated hemoglobin.
Percentage of participants with at least one symptomatic hypoglycemic adverse event, excluding data after initiation of glycemic rescue therapy.
Hemoglobin A1c (HbA1c) is a measure of glycated hemoglobin in the blood. HbA1c greater than 6.5% was considered inadequately controlled.
Week 24 A1C minus baseline (Week 0) A1C. The unit for A1C is "percent". Thus, this measure represents a difference of percent values.
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 12 HbA1c percent minus the Week 0 HbA1c percent.
Hemoglobin A1C (A1C) is measured as percent. Thus this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.
Hemoglobin A1C (A1C) is measured as percent. Thus this change from baseline reflects the Week 18 A1C percent minus the Week 0 A1C percent.
Safety and tolerability were measured in terms of the number of patients with clinical adverse experiences (CAEs), serious CAEs, drug-related CAEs, laboratory adverse experiences (LAEs), serious LAEs, and drug-related LAEs. Drug-relationship was assessed by the study investigator according to his/her best clinical judgment.
HbA1c is measured as percent. Thus, this change from baseline reflects the Week 52 HbA1c percent minus the Week 0 HbA1c percent.
A1C is measured as a percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.
HbA1c is measured as a percent. Thus, this change from baseline reflects the Week 24 HbA1c percent minus the Week 0 HbA1c percent.
Glucose total AUC 0-2 hours for MTT was measured at Baseline (Week 0) and at Week 8. After fasting for ≥10 hours, blood samples for glucose measurement were drawn at 0 minutes (at standard meal loading), 30 minutes, 60 minutes, 90 minutes, and 120 minutes. At Week 8, participants received study drug or placebo 30 minutes prior to consuming a standard meal.
An 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 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.
Change from baseline at Week 4 is defined as 24-hour weighted mean glucose (24hr-WMG) at Week 4 minus 24hr-WMG at Week 0.
This study will investigate the effects of sitagliptin, a medicine commonly used to treat type 2 diabetes, on the utilization of glucose by the heart in patients with heart failure which is not due to heart attacks. We hope to determine whether improving the heart's ability to use glucose in the blood may help improve the function of the heart as well. If so, this may suggest that even people who do not have frank diabetes but who do have heart failure may benefit from using this medication. Baseline glucose uptake scans will be compared with the scans on sitagliptin thirty days after baseline
This study will investigate the effects of sitagliptin, a medicine commonly used to treat type 2 diabetes, on the utilization of glucose by the heart in patients with heart failure which is not due to heart attacks. We hope to determine whether improving the heart's ability to use glucose in the blood may help improve the function of the heart as well. If so, this may suggest that even people who do not have frank diabetes but who do have heart failure may benefit from using this medication.
| Arm | Type | Description |
|---|---|---|
| Sitagliptin | EXPERIMENTAL | Participants will receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants will continue to receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Placebo/Metformin | PLACEBO_COMPARATOR | Participants will receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants will receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Metformin | ACTIVE_COMPARATOR | Participants will receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants will continue to receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Placebo/Sitagliptin | PLACEBO_COMPARATOR | Participants will receive 1 tablet of placebo matching sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 0-20. Participants will receive 1 tablet of sitagliptin 100 mg prior to the morning meal and 2 tablets of placebo matching metformin 500 mg prior to both the morning and evening meals during Weeks 20-54. |
| Sitagliptin +/- glimepiride | EXPERIMENTAL | Sitagliptin 100 mg tablet orally once daily for 26 weeks. Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have received glimepiride orally for glycemic control. |
| Liraglutide | ACTIVE_COMPARATOR | Liraglutide subcutaneous injection once daily for 26 weeks (starting dose 0.6 mg daily up-titrated to 1.2 mg daily on Day 8). Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have had their liraglutide dose uptitrated to 1.8 mg daily for glycemic control. |
| Sitagliptin/Sitagliptin | EXPERIMENTAL | - |
| 1 | EXPERIMENTAL | sitagliptin |
| 2 | ACTIVE_COMPARATOR | glimepiride |
| Sitagliptin 25 mg | EXPERIMENTAL | - |
| Glipizide 2.5 mg - 20 mg | ACTIVE_COMPARATOR | - |
| Glipizide | ACTIVE_COMPARATOR | Glipizide + Placebo for Sitagliptin |
| Sitagliptin with Standard of Care | EXPERIMENTAL | Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: No specific intervention (standard recommendation) on physical exercise and diet. |
| Sitagliptin with Diet Advice | EXPERIMENTAL | Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet which includes advice on diet with a leaflet and a diary |
| Sitagliptin with Diet and Physical Activity Advice | EXPERIMENTAL | Subjects received sitagliptin 100 mg once daily for 26 Weeks, and: Intervention on diet + physical activity which includes advice on diet and physical activity with leaflets and diaries PLUS advice on physical activity with the utilization of a pedometer: subjects were asked to walk 10,000 steps per day 5 or more days per week. |
| 3 | ACTIVE_COMPARATOR | metformin |
| Sitagliptin 50 mg QD | EXPERIMENTAL | sitagliptin 50 mg orally once daily (QD=once daily) |
| Voglibose 0.2 mg TID | ACTIVE_COMPARATOR | voglibose 0.2 mg orally three times daily (TID= three times daily) |
| Placebo/ Pioglitazone | PLACEBO_COMPARATOR | Placebo tablet daily for 24 weeks followed by Pioglitazone tablet daily for 30 weeks |
| Sitagliptin 100 mg | EXPERIMENTAL | Sitagliptin 100 mg |
| Sitagliptin 200 mg | EXPERIMENTAL | Sitagliptin 200 mg |
| Placebo/Pioglitazone | PLACEBO_COMPARATOR | Placebo/Pioglitazone |
| Placebo | PLACEBO_COMPARATOR | Participants in the Placebo treatment sequence will receive placebo to sitagliptin in Phase A and glipizide in Phase B. |
| Placebo / Glipizide 5 mg | PLACEBO_COMPARATOR | The Placebo/Glipizide 5 mg group includes patients who were administered once-daily treatment with oral tablets of sitagliptin-matched placebo during Phase A (Weeks 0-24) of the treatment period. During Phase B (Weeks 24-104) of the treatment period these patients received once-daily coadministered treatment with oral tablets of sitagliptin-matched placebo 100 mg and glipizide 5 mg which was allowed to be uptitrated, in a blinded fashion, to a maximum dose of 15 mg/day. |
| Sitagliptin 100 mg/100 mg | ACTIVE_COMPARATOR | Phase A and B: Oral tablets of sitagliptin 100 mg Once a Day (q.d ) |
| Sitagliptin 200 mg/200 mg | ACTIVE_COMPARATOR | Phase A and B: Oral tablets of sitagliptin 200 mg q.d |
| Placebo/Sitagliptin 100 mg | PLACEBO_COMPARATOR | Phase A: Oral tablets of placebo matching sitagliptin 100 mg q.d. Phase B: Oral tablets of sitagliptin 100 mg q.d. |
| Placebo/Sitagliptin 200 mg | PLACEBO_COMPARATOR | Phase A: Oral tablets of placebo matching sitagliptin 200 mg q.d. Phase B: Oral tablets of sitagliptin 200 mg q.d. |
| Sitagliptin 50 mg | EXPERIMENTAL | Participants will take one tablet of sitagliptin 50 mg and one tablet of placebo for sitagliptin 25 mg orally once daily for 8 weeks. |
| Sitagliptin 25 mg once daily | EXPERIMENTAL | Sitaglipin (MK-0431), 25 mg, once daily for 12 weeks, orally. Due to interim analysis of this study and another Phase IIB study, participants in this arm were switched into the 100-mg once daily arm during either the first or initiation of the second extensions study periods. |
| Sitagliptin 50 mg once daily | EXPERIMENTAL | Sitagliptin, 50 mg, once daily for 12 weeks, orally. Due to interim analysis of this study and another Phase IIB study, participants in this arm were switched into the 100-mg once daily arm during either the first or initiation of the second extensions study periods. |
| Sitaglipin 100 mg once daily | EXPERIMENTAL | Sitagliptin, 100 mg, once daily for 158 weeks, orally |
| Sitagliptin 50 mg twice daily | EXPERIMENTAL | Sitagliptin 50 mg, twice daily for 12 weeks, orally. Due to interim analysis of this study and another Phase IIB study, participants in this arm were switched into the 100-mg once daily arm during either the first or initiation of the second extensions study periods. |
| Placebo to Sitagliptin → Metformin | PLACEBO_COMPARATOR | Placebo to Sitagliptin, once daily, orally for 12 weeks. Participants randomized to the placebo treatment group during the base study were reallocated to treatment with metformin 850 mg twice daily (b.i.d., initiated with 850 mg q.d. for 4 weeks then force titrated to 850 mg b.i.d.) during either the first or initiation of the second extensions study periods. |
| All subjects recieve Sitagliptin | EXPERIMENTAL | All subjects are aware of what they are taking. Nobody is blinded in this study. study |
| Name | Type | Description |
|---|---|---|
| Sitagliptin | DRUG | Sitagliptin 100 mg tablet administered orally once daily |
| Metformin | DRUG | Metformin 500 mg tablets administered orally starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily |
| Placebo to sitagliptin | DRUG | Matching placebo to sitagliptin 100 mg tablet administered orally once daily |
| Placebo to metformin | DRUG | Matching placebo to metformin 500 mg tablets, 2 tablets administered orally twice daily |
| Glycemic Rescue 1 | DRUG | Participants in the sitagliptin arm who require glycemic rescue will receive metformin during Weeks 0-20 and Weeks 20-54. Participants in the placebo arm who require glycemic rescue will receive metformin during Weeks 0-20. Participants in the placebo arm who have switched to metformin during Weeks 20-54 and require glycemic rescue will receive sitagliptin. |
| Glycemic Rescue 2 | BIOLOGICAL | Participants who require glycemic rescue after Glycemic Rescue 1 will receive open-label insulin. Participants on background insulin therapy will have the dose of their background insulin up-titrated. |
| liraglutide | DRUG | 0.6 mg by subcutaneous (pen) injection, once daily, on Days 1-7; up-titrated on Day 8 to 1.2 mg daily. At Week 12, dose may be increased to 1.8 mg once daily for participants who did not meet protocol-specified glycemic goals. |
| glimepiride | DRUG | starting dose of 1 mg tablet (up-titrated as needed), once daily, as needed, after Week 12. |
| Comparator: Placebo | DRUG | Placebo to sitagliptin once daily for 12 weeks (double-blind period) |
| Voglibose | DRUG | All participants received a stable dose of voglibose, in accordance with the package insert, throughout the study. |
| Comparator: glimepiride | DRUG | glimepiride 1 mg per day to be up-titrated (up to week 18 of the double-blind treatment period) as considered appropriate by the investigator, based upon the results of patient's self blood glucose monitoring (SBGM). The maximum dose of glimepiride must not be higher than 6 mg/day. |
| open-label metformin | DRUG | open-label metformin oral tablets (≥1500 mg/day) in addition to Glimepiride or Sitagliptin treatment. |
| Placebo | DRUG | Placebo for 6 weeks |
| Glipizide | DRUG | 2.5 mg (1/2 of a 5-mg tablet) once daily, up to 10 mg twice daily (four 5-mg tablets), for a maximum of 20 mg |
| Placebo for Sitagliptin | DRUG | Participants with moderate renal insufficiency will receive 2 placebo for sitagliptin tablets orally daily; participants with severe renal insufficiency will receive 1 placebo for sitagliptin tablet orally daily |
| Placebo for Glipizide | DRUG | Participants will receive 1/2 tablet of placebo for glipizide orally once daily up to 2 tablets orally twice daily |
| sitagliptin phosphate | DRUG | sitagliptin 100 mg once daily. Duration of treatment: 26 Weeks |
| Comparator: Diet | BEHAVIORAL | Diet |
| Comparator: Physical Activity | BEHAVIORAL | Physical Activity |
| Comparator: metformin | DRUG | metformin 850 mg Twice a day (BID) for 24 weeks |
| Comparator: Antidiabetic Standard of Care | DRUG | Patient can take any oral antidiabetic drug (other than metformin) |
| Comparator: voglibose | DRUG | voglibose 0.2 mg orally three times daily TID. Duration of Treatment: 12 Weeks |
| Comparator: Sitagliptin | DRUG | sitagliptin 10 mg tablet, once daily for 54 weeks |
| Comparator: Pioglitazone | DRUG | Pioglitazone 30 mg tablet once daily for 30 weeks |
| Comparator: sitagliptin 100 mg | DRUG | sitagliptin 100 mg oral tablet once daily for 54 weeks |
| Comparator: sitagliptin 200 mg | DRUG | sitagliptin 200 mg (2- 100 mg oral tablets) once daily for 54 weeks |
| Placebo to glipizide | DRUG | One placebo to glipizide 5 mg tablet per day. The dose of placebo to glipizide administered per day may be increased after 2 weeks and at 2-week intervals thereafter up to 20 mg based upon fingerstick glucose determinations. |
| sitagliptin (MK0431) | DRUG | Sitagliptin 100 mg oral tablets of sitagliptin once daily. |
| Comparator: glipizide | DRUG | Glipizide 1 tablet (5 mg) per day. Patients could then up-titrated to a total daily dose of 4 tablets twice daily (20mg/day) based on their glycemic control. |
| Placebo/Glipizide 5 mg | DRUG | Placebo (to match Sitagliptin 100 mg) from Visit 4 through Visit 8; Glipizide 5 mg from Visit 8, week 24 to Final Visit (Week 104) |
| Pioglitazone | DRUG | Pioglitazone 15 mg once daily, for patients not meeting specific glycemic goals during the placebo-controlled treatment period \[Phase A\], from Visit 5 (Week 6) to Visit 8 (Week 24) |
| Metformin - Rescue | DRUG | Phase A: Patients not meeting specific glycemic goals will receive open-label metformin as 500 mg, 850 mg, and 1000 mg oral tablets titrated at the discretion of the investigator. Phase B: These patients will not initiate Phase B double-blind medication. |
| Placebo for Sitagliptin 25 mg | DRUG | 1 tablet orally once daily before breakfast for 8 weeks |
| Placebo for Sitagliptin 50 mg | DRUG | 1 tablet orally once daily before breakfast for 8 weeks |
| Sitagliptin 25 mg | DRUG | 1 tablet orally once daily before breakfast for 8 weeks |
| Sitagliptin 50 mg | DRUG | 1 tablet orally once daily before breakfast for 8 weeks |
| Rescue | DRUG | Patients whose FPG \>240 mg/dL from Week 16 or HbA1C \>8.5% from Week 25 up to (not including) Week 52 could receive rescue antihyperglycemic therapy with pioglitazone, and remain in the extension study (Extension 1). Participants were eligible for rescue with pioglitazone 30 mg (or rosiglitazone in countries where pioglitazone was not licensed) if they met the following criteria: from Week 16 and during the second extension: FPG consistently \>240 mg/dL (repeated and confirmed within 3 to 7 days); from Week 52 up to (not including) Week 70: HbA1C \>8%; from Week 70 up to (not including) Visit 21/Week 106: HbA1C \>7.5% (Extension 2). Participants placed on rescue therapy with pioglitazone (rosiglitazone where pioglitazone is not available) in the first or second extensions were not eligible for enrollment in the third extension. Rescue therapy was not available in the third extension. |
Inclusion Criteria: * Type 2 Diabetes Mellitus (T2DM) * Has not received treatment with an antihyperglycemic agent (AHA) for ≥12 weeks prior to the Screening Visit/Visit 1, or is on a stable dose of insulin (without any other AHA) for at least 12 weeks prior to the Screening Visit/Visit 1. At scree...
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.