The Benefits of Metformin Therapy During Continuous Subcutaneous Insulin Infusion Treatment of Type 1 Diabetic Patients

Abstract

OBJECTIVE -This study was designed to assess the insulin-sparing effect of oral administration of metformin along with a continuous subcutaneous insulin infusion (CSII) for the treatment of type 1 diabetic patients.RESEARCH DESIGN AND METHODS -A total of 62 patients (25 women and 37 men) were studied in a monocenter, randomized, double-blind placebo-controlled study, comparing metformin (850 mg b.i.d.) with placebo in association with CSII during a 6-month period.RESULTS -Treatment with metformin was associated with a reduction in daily insulin requirements between V0 and V6 of Ϫ4.3 Ϯ 9.9 units (Ϫ7.8 Ϯ 18%) compared with an increase with placebo treatment of 1.7 Ϯ 8.3 units (2.8 Ϯ 12.7%) (P ϭ 0.0043). A decrease in basal requirement of insulin was also observed in patients treated with metformin of Ϫ2.6 Ϯ 3.2 units (Ϫ7.9 Ϯ 23.8%) compared with an increase with placebo treatment of 1.9 Ϯ 5.7 units (8.8 Ϯ 27.1%) (P ϭ 0.023). HbA 1c remained unchanged in treatment with metformin and placebo between V0 and V6. The number of hypoglycemic events (Ͻ60 mg/dl) was similar in both groups. Significant reductions of total cholesterol (P ϭ 0.04) and LDL cholesterol (P ϭ 0.05) were observed in patients treated with metformin. Gastrointestinal events, including diarrhea and abdominal pain, were reported in three patients in the metformin group who discontinued the trial. Mild or moderate gastrointestinal side effects were also reported in eight patients treated with metformin and two patients treated with placebo (P ϭ 0.069).CONCLUSIONS -Metformin was found to be a safe insulin-sparing agent, when used in combination with CSII for the treatment of type 1 diabetes.

The use of metformin in type 1 diabetes: a systematic review of efficacy

“…Of the remaining 12 publications, one concerned insulin-requiring type 2 diabetes rather than type 1 diabetes (noted after translation) [61], and one covered a treatment period of fewer than 7 days [62]. Only ten studies were therefore identified [16,17,20,21,23,25,26,[63][64][65]. One of these, which was conducted on participants living in a children's home and did not mention informed consent, was excluded from further analysis [64].…”

“…The final nine studies [16,17,20,21,23,25,26,63,65] covered a total of 192.8 patient years, and the number of completed participants ranged from ten to 92 (median 26) (two studies did not report number completed [17,26]) ( Table 1). The total maximum daily metformin dose varied from 1,000 to 2,550 mg; duration of therapy ranged from 7 days to 12 months (median 4 months).…”

“…[61] • Duration of treatment <7 days (n=1) [62] Randomised metformin trials in adults with type 1 diabetes (n=10) [16,17,20,21,23,25,26,[63][64][65] No informed consent (n=1) [64] Intervention trials meeting inclusion criteria (n=9) [16,17,20,21,23,25,26,63,65] Gin [25] 1985 Full 1,700…”

Double Diabetes: The Search for a Treatment Paradigm in Children and Adolescents

“…One such strategy is the addition of a drug that improves insulin sensitivity such as metformin, a biguanide that acts principally by increasing insulin sensitivity in the liver by inhibiting hepatic gluconeogenesis and thereby reducing hepatic glucose production [75]. Other minor mecha-nisms include decreasing fatty acid oxidation and intestinal glucose absorption [76], and increasing peripheral insulin sensitivity by enhancing glucose uptake in the muscles [77]. Metformin has mainly been used in adult patients with T2D and several studies have shown beneficial effects on body weight, blood lipid levels and metabolic control [78][79][80].…”

“…Randomized controlled trials with metformin in adolescents with T2D reported an improvement in fasting plasma glucose level [81]. However, there have been conflicting reports from studies in adolescents with T1D [75][76][77]82,83]. The benefit was transient in one study [83] and negative in another [82].…”