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

Stable-weight Profile

Weight gain is one of the main setbacks associated with several OADs. In a 1-year, open-label study comparing therapeutic equivalence of repaglinide versus glyburide, Marbury et al. showed that treatment with repaglinide was as safe and effective as glyburide.[70] No significant differences in mean body weight were observed between treatment groups (repaglinide: -0.22 kg; glyburide: +0.05 kg). While the glycemic effect was most pronounced in pharmacotherapy-naive patients, treatment with repaglinide led to less weight gain (+2.45 kg) when compared with treatment with glyburide (+3.64 kg; no p-value provided).

In keeping with these observations, Wolffenbuttel et al. have shown in another study that, in contrast to glyburide, repaglinide demonstrated a stable weight profile, with negligible weight gain from baseline to end of the 12-month follow-up period.[71] Similar results were demonstrated by Derosa et al. in a study comparing effects of repaglinide and glimepiride on overall glycemic control.[72] Body weight remained stable across the study when compared with baseline values in both treatment groups.

Little or no weight gain was associated with repaglinide plus metformin therapy; Soegondo et al. showed that body weight in response to treatment with repaglinide alone or in combination with metformin did not change significantly from baseline.[65] Moses et al. demonstrated that body weight remained stable in a group on metformin alone but increased in the repaglinide and combined therapy groups (2.4 ± 0.5 and 3.0 ± 0.5 kg, respectively; p < 0.05).[63] In a study comparing the safety and efficacy of repaglinide versus nateglinide when used in combination with metformin, Raskin et al. demonstrated that both repaglinide and nateglinide showed small weight changes from baseline (0.6 kg gain vs 0.5 kg loss, respectively).[64] In a study investigating the safety and efficacy of repaglinide as monotherapy or in combination with metformin, Shapiro et al. demonstrated that there was an overall mean reduction in weight in all patients of 1.1 ± 0.3 kg (p < 0.0001).[66]

The beneficial effect of metformin treatment on body weight, consisting of weight loss or weight-neutral effects, is a well-established advantage as confirmed by results from UKPDS 34[15] and further supported by A Diabetes Outcome Progression Trial (ADOPT) trial.[73] In ADOPT, the weight loss associated with metformin treatment was maintained over 5 years of follow-up. These data indicate that combination therapy of repaglinide plus metformin provides efficacy comparable to other metformin-based combination therapies and has a favorable safety profile.


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