Intensive insulin therapy combined with metformin in obese type 2 diabetec patients

Abstract

Unlike other pharmacological therapies used in obese type 2 diabetic patients, metformin has been shown to improve glycemic control with lower insulin levels and not to involve weight gain. We therefore examined the effect of adjunct metformin in 13 severely obese type 2 diabetic patients (BMI 39.3 +/- 3.9 kg/m2) in suboptimal glycemic control pretreated with intensified insulin therapy. Patients were randomly assigned to either metformin or placebo treatment (double-blind) for 10 weeks and after a 2 week washout period received the opposite treatment, respectively, for 10 additional weeks. HbA1c decreased comparably during placebo (from 8.1 +/- 0.4 to 7.6 +/- 0.3%) and metformin (from 8.5 +/- 0.4 to 7.4 +/- 0.3%, p = 0.29 vs. placebo). Changes in fasting glucose levels were also not different between placebo (from 9.3 +/- 0.7 to 9.5 +/- 0.7 mM) and metformin (from 10.3 +/- 0.5 to 9.5 +/- 0.6 mM, p = 0.44 vs. placebo). Total exogenous insulin requirements decreased from 53 +/- 10 to 35 +/- 7 units during metformin treatment (p = 0.02 vs. placebo). Changes in fasting insulin levels during placebo and metformin treatments were not different (p = 0.11). Metformin had no effect on body weight and serum triglycerides but marginally decreased serum cholesterol levels (from 239 +/- 18 to 211 +/- 14 mg/dl, p = 0.005, p = 0.08 vs. placebo). During the oral glucose tolerance test no differences were observed in the areas under the curve for glucose and insulin while that for C-peptide showed a tendency to increase during metformin administration. We conclude that addition of metformin to insulin treatment in severely obese type 2 diabetic patients improves glycemia but not hyperinsulinemia in comparison to intensive insulin therapy alone. With adjunct metformin, approximately 30% less exogenous insulin is required. With respect to glycemia and lipids, adjunct metformin can be a reasonable treatment alternative in selected obese patients with type 2 diabetes already on intensive insulin therapy.

The effects of long-term metformin treatment on adrenal and ovarian steroidogenesis in women with polycystic ovary syndrome

“…We are aware of a study (31) finding no change in either basal or stimulated levels of C peptide in a group of hypertensive patients after metformin. In a group of obese type 2 diabetics an increase in C peptide levels after metformin treatment was found (32). These discrepancies are difficult to explain and deserve further research.…”

Metformin and body weight

“…A number of these trials, listed in Table 2, 54-66 demonstrated significant reductions in body weight between patients receiving insulin and metformin compared with insulin and placebo 54,56,59,60,62 although other studies did not. 55,57,58,61,63,64 Two trials demonstrated Figure 1 Effects of randomized treatments on body weight in overweight patients in the UK Prospective Diabetes Study. 31 …”

Medikamentöse Therapie des Diabetes mellitus Typ 2

“…Es existiert eine Reihe von Publikationen über deren Wirksamkeit in Bezug auf HbA1c-Senkung (effektiver als Insulin allein), Nüchterblutzuckersen-kung und insulinsparendem Effekt [22]. Die Gabe von Metformin zur Nacht (Suppression der nächt-lichen Glukoneogenese) in Kombination mit Insulin ist v. a. für adipöse Patienten mit ausgeprägter Insulinresistenz geeignet [23], da sich in dieser Kombination neben einem positiven Effekt auf die Stoffwechseleinstellung Insulin einsparen lässt und der Gewichtsverlauf positiv beeinflusst wird [24]. Auch die Kombination mit α-Glukosidase-Hemmern erscheint für adipöse Typ-2-Diabetiker mit ausgeprägter Insulinresistenz sinnvoll.…”