Table 24

Summary evidence table for sitagliptin

Type 2 DiabetesQuality of evidenceConclusion
Key Question 1. For children and adults with type 2 diabetes, does sitagliptin differ in efficacy, effectiveness, and in harms when compared to placebo, when compared to other hypoglycemic agents as monotherapy, or when added to other hypoglycemic agents?Evidence in children is lacking.
EffectivenessNo available data-No studies assessed long-term health outcomes and none were > 52 weeks in duration.
EfficacyMonotherapy compared with placebo
-Fair, 5 RCTs



Monotherapy compared with an oral hypoglycemic agent
-Fair, 2 RCTs



Combined therapy compared with placebo
-Fair, 4 RCTs



Combined therapy compared with oral hypoglycemic agents
-Fair-Poor, 1 RCT
-Evidence on time-to-treatment-failure is lacking.

Monotherapy compared with placebo
-Sitagliptin significantly improved A1c, FPG, and PPG relative to placebo.

Pooled data for the above:
A1c: −0.81% (95% CI, −0.94 to −0.67)
FPG: −24.4 mg/dL (95% CI, −29.5 to −19.3)
PPG: −54.5 mg/dL (95% CI, −65.5 to −43.5)


-Sitagliptin-treated patients lost slightly less weight compared with placebo-treated patients (range: −0.1 to −0.6 kg compared with −0.7 to −1.1 kg; pooled: +0.62 kg (95% CI, +0.36 to+0.89)

Monotherapy compared with an oral hypoglycemic agent-Though formal statistical analyses were not conducted for glipizide-or metformin monotherapy compared with sitagliptin monotherapy, it appears that sitagliptin may be comparable to glipizide and metformin 1 g/d in lowering A1c based on qualitative evaluation of the magnitude of difference between groups. Additional trials are needed to verify the findings.

Ranges for sitagliptin monotherapy compared with glipizide and metformin monotherapies:
A1c: −0.54% to −0.66% compared with −0.8% to −1.1%
FPG: −18 mg/dL compared with −25 to −29 mg/dL
PPG: −48 to −59 mg/dL compared with −53 to −78 mg/dL


-Weight remained unchanged for sitagliptin while weight gain (+0.9 kg) occurred for those on glipizide. Weight loss occurred with metformin by about 1 kg.

Combined therapy compared with placebo
-The addition of sitagliptin to one or two oral hypoglycemic agents was more effective for glycemic control than the addition of placebo.

Combined therapy compared with oral hypoglycemic agents
-There was no difference in A1c between regimens that included the addition of sitagliptin or glipizide to metformin. Sitagliptin- treated patients experienced slightly more weight loss (−1.5 kg) than compared with weight gain seen in glipizide-treated patients (+1.5 kg).
-There were no significant differences in the reduction in A1c for those on sitagliptin or rosiglitazone added to metformin monotherapy (between-group difference: −0.06%, 95% CI −0.25 to +0.14%) at 18 weeks.
HarmsMonotherapy compared with placebo
-Fair, 5 RCTs



Monotherapy compared with an oral hypoglycemic agent
-Fair, 2 RCTs



Combined therapy compared with placebo
-Fair, 4 RCTs



Combined therapy compared with oral hypoglycemic agents
-Fair-Poor, 1 RCT
- Studies beyond 52 weeks in duration evaluating harms are lacking.

Monotherapy compared with placebo
-Fewer sitagliptin-treated patients than placebo-treated patients withdrew due to adverse events.
-There was no statistically significant difference in the risk of hypoglycemia between sitagliptin and placebo groups (pooled relative risk 1.21, 95% CI 0.42 to 3.5).
- There were no statistically significant differences between sitagliptin monotherapy and placebo in the risk of abdominal pain, nausea, vomiting, or diarrhea.

Pooled relative risks:
Abdominal pain: RR 1.17, 95% CI 0.54–2.52
Nausea: RR 1.56, 95% CI 0.53–4.57
Vomiting: pooled RR 0.65, 95% CI 0.18–2.4
Diarrhea: RR 1.26, 95% CI 0.64–2.25

Monotherapy compared with an oral hypoglycemic agent
-Sitagliptin and metformin had a lower incidence of hypoglycemia than glipizide.
-Sitagliptin had lower rates of abdominal pain, nausea, vomiting, and diarrhea than metformin.

Combined therapy compared with placebo
- Regimens that included sulfonylurea ± sitagliptin exhibited greater risk of hypoglycemia than therapies without sulfonylurea.
-Combination therapies of sitagliptin with sulfonylurea, thiazolidinedione, and metformin had slightly greater rates of abdominal pain, nausea, vomiting, and diarrhea than the individual oral hypoglycemic agents as monotherapy.

Combined therapy compared with oral hypoglycemic agents
-Sitagliptin added to metformin had lower rates of hypoglycemia than glipizide added to metformin.
- Sitagliptin + metformin versus glipizide + metformin showed minimal difference in the incidence of abdominal pain, nausea, vomiting, and diarrhea.
Key Question 2. Are there subgroups of patients for which sitagliptin is more or less suitable than other hypoglycemic agents?-Fair-Poor-In general, it appears that there are no significant differences in treatment effect based on age, sex, BMI, race. Data on file from 1 trial showed that Hispanic patients showed slightly larger reductions in A1c than White or “Other” patients.
- Patients with higher baseline A1c ≥9% tended to exhibit larger treatment effects than patients with baseline A1c <8%.
-Patients with <3 years’ duration of diabetes tended to exhibit larger treatment effects than those with > 3 years’ duration of diabetes.

Abbreviations: CI, confidence interval; FPG, fasting plasma glucose; PPG, postprandial glucose; RCT, randomized controlled trial.

From: Results

Cover of Drug Class Review: Newer Drugs for the Treatment of Diabetes Mellitus
Drug Class Review: Newer Drugs for the Treatment of Diabetes Mellitus: Final Report [Internet].
Norris SL, Lee NJ, Severance S, et al.
Portland (OR): Oregon Health & Science University; 2008 Aug.
Copyright © 2008, Oregon Health & Science University, Portland, Oregon.

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