Combination Therapy for Patients with Type 2 Diabetes: Repaglinide in Combination with Metformin

Robert G Moses


Expert Rev Endocrinol Metab. 2010;5(3):331-342. 

In This Article

Safety & Tolerability

Combination therapy of repaglinide plus metformin has been demonstrated to be safe and well tolerated in the treatment of T2DM after an unsatisfactory response to OAD monotherapy.[17]

In clinical trials of repaglinide, hypoglycemia is the most common (occurring in >5% of patients) adverse reaction leading to withdrawal of patients.[103] Gastrointestinal reactions (e.g., diarrhea, nausea, vomiting) are the most common adverse reactions (>5%) with metformin HCl.[103] Bech et al. demonstrated that initiation of prandial repaglinide is well accepted and is associated with a significant improvement in treatment satisfaction.[74]

The safety findings from studies of repaglinide plus metformin showed a comparable incidence of adverse events, including gastrointestinal complications, when compared with metformin monotherapy.[61] Greater-than-additive effects of the repaglinide and metformin combination may also help reduce adverse events seen with high doses of metformin treatment.[61] Results of clinical studies have shown a low incidence of hypoglycemic episodes with repaglinide plus metformin combination therapy, with most episodes being mild.[61,65] Data from several clinical studies have shown that repaglinide caused fewer episodes of hypoglycemia and severe reactions than SUs (0.57 vs 1.01%).[75] In addition, the rate of withdrawal from clinical studies due to hypoglycemia was reduced in repaglinide-treated patients. No instances of hospitalization, coma or death were reported in any patient treated with repaglinide.

In an open-label, parallel-group study, combination repaglinide plus metformin showed higher blood glucose values during hypoglycemic events and fewer events at glucose levels of less than 55 mg/dl (3 mmol/l) when compared with patients receiving a combination of glyburide plus metformin.[68] Shapiro et al. have also reported a decline in perceived episodes of hypoglycemia and a simultaneous decrease in the 'need to snack' to avert hypoglycemic episodes in patients who were previously taking SUs and later randomized to the repaglinide treatment arm.[66]


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