Sitagliptin in Combination with Metformin and Insulin

In a 24-week placebo-controlled study of sitagliptin 100mg as add-on therapy in patients with type 2 diabetes inadequately controlled on metformin and insulin (sitagliptin, N=229; placebo, N=233), the only adverse reaction reported regardless of investigator assessment of causality in ≥5% of patients treated with sitagliptin and more commonly than in patients treated with placebo was hypoglycemia (Table 3).

Hypoglycemia

In all (N=5) studies, adverse reactions of hypoglycemia were based on all reports of symptomatic hypoglycemia; a concurrent glucose measurement was not required although most (77%) reports of hypoglycemia were accompanied by a blood glucose measurement ≤70 mg/dL. When the combination of sitagliptin and metformin was co-administered with a sulfonylurea or with insulin, the percentage of patients reporting at least one adverse reaction of hypoglycemia was higher than that observed with placebo and metformin co-administered with a sulfonylurea or with insulin (Table 3).

Table 3: Incidence and Rate of Hypoglycemia* (Regardless of Investigator Assessment of Causality) in Placebo-Controlled Clinical Studies of Sitagliptin in Combination with Metformin Co-administered with Glimepiride or Insulin *
Adverse reactions of hypoglycemia were based on all reports of symptomatic hypoglycemia; a concurrent glucose measurement was not required: Intent-to-treat population.
†
Based on total number of events (i.e., a single patient may have had multiple events).
‡
Severe events of hypoglycemia were defined as those events requiring medical assistance or exhibiting depressed level/loss of consciousness or seizure.
Add-On to Glimepiride +
Metformin (24 weeks) Sitagliptin 100mg

+ Metformin

+ Glimepiride Placebo

+ Metformin

+ Glimepiride
 N = 116  N = 113
Overall (%) 19 (16.4) 1 (0.9)
Rate (episodes/patient-year)† 0.82 0.02
Severe (%)‡ 0 (0.0) 0 (0.0)
Add-On to Insulin
+ Metformin (24 weeks) Sitagliptin 100mg

+ Metformin

+ Insulin Placebo

+ Metformin

+ Insulin
 N = 229 N = 233
Overall (%) 35 (15.3) 19 (8.2)
Rate (episodes/patient-year)† 0.98 0.61
Severe (%)‡ 1 (0.4) 1 (0.4)

The overall incidence of reported adverse reactions of hypoglycemia in patients with type 2 diabetes inadequately controlled on diet and exercise was 0.6% in patients given placebo, 0.6% in patients given sitagliptin alone, 0.8% in patients given metformin alone, and 1.6% in patients given sitagliptin in combination with metformin. In patients with type 2 diabetes inadequately controlled on metformin alone, the overall incidence of adverse reactions of hypoglycemia was 1.3% in patients given add-on sitagliptin and 2.1% in patients given add-on placebo.

In the study of sitagliptin and add-on combination therapy with metformin and rosiglitazone, the overall incid