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.
In clinical trials of repaglinide, hypoglycemia is the most common (occurring in >5% of patients) adverse reaction leading to withdrawal of patients. Gastrointestinal reactions (e.g., diarrhea, nausea, vomiting) are the most common adverse reactions (>5%) with metformin HCl. Bech et al. demonstrated that initiation of prandial repaglinide is well accepted and is associated with a significant improvement in treatment satisfaction.
The safety findings from studies of repaglinide plus metformin showed a comparable incidence of adverse events, including gastrointestinal complications, when compared with metformin monotherapy. Greater-than-additive effects of the repaglinide and metformin combination may also help reduce adverse events seen with high doses of metformin treatment. 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%). 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. 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.
Expert Rev Endocrinol Metab. 2010;5(3):331-342. © 2010 Expert Reviews Ltd.
Cite this: Combination Therapy for Patients with Type 2 Diabetes: Repaglinide in Combination with Metformin - Medscape - May 01, 2010.