Metformin for obese, insulin-treated diabetic patients: improvement in glycaemic control and reduction of metabolic risk factors

Giugliano, Dario; Quatraro, A; Consoli, G; Minei, A.; Ceriello, Antonio; Rosa, Nicoletta De; D'Onofrio, F

doi:10.1007/bf00315466

Cited by 159 publications

(79 citation statements)

References 26 publications

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“…Glycaemic control improved similarly in both groups. In keeping with previous data, metformin had an insulin sparing effect, i. e. less insulin was required in the MET + than the MET± group for a similar decrease in blood glucose concentrations [16]. In the entire group, improvement in glycaemia favoured weight gain by decreasing the energy lost in the urine as glucose and by decreasing BMR.…”

Section: Discussionsupporting

confidence: 86%

Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus

1999

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Despite a good initial response to insulin therapy in patients with Type II (non-insulin-dependent) diabetes mellitus, long-term treatment results are often less satisfactory [1]. The poor treatment results have been attributed to the progressive nature of Type II diabetes and to failure to increase the insulin dose sufficiently to overcome insulin resistance induced by weight gain [2,3]. Previous data on the causes of weight gain during insulin therapy in patients with Type II diabetes are sparse. In one study the basal metabolic rate (BMR) was measured before and after 1 year of insulin therapy in eight patients with Type II diabetes, whose weight increased by 3.9 kg, HbA 1 c decreased by 1.7 % and absolute BMR (kJ/ min) remained unchanged [4]. BMR also remained unchanged in a study of six patients treated for 2 weeks with glyburide and insulin [5]. Glucosuria or dietary intake were not determined in these studies. Another previous study found body weight to increase by 2.1 kg during combination therapy with sulfonylurea and bedtime insulin and attributed this increase to a reduction in glucosuria but data on BMR or dietary intake were not reported [6]. Diabetologia (1999) 2 ) were treated with insulin alone (n = 13) or insulin and with metformin (n = 13). Components of energy balance (basal metabolic rate, energy intake, glucosuria) were measured at 0 and 12 months. Results. Glycaemic control improved similarly in patients using (HbA 1 c 10.5 ± 0.3 vs 7.6 ± 0.2 %, p < 0.001) and not using (10.2 ± 0.3 vs 7.8 ± 0.3 %, p < 0.001) metformin. The metformin group required 47 % less insulin than the group not using metformin (p < 0.001). Body weight increased by 3.8 ± 0.8 and 7.5 ± 1.6 kg (p < 0.05), respectively. Basal metabolic rate and glucosuria were similar at 0 and 12 months in both groups but the metformin group decreased energy intake by 1.12 ± 0.46 MJ/day, whereas it remained unchanged in the other group (0.15 ± 0.42 MJ/day). Changes in body weight and glycaemia were statistically significant independent determinants of basal metabolic rate. Their change in opposite directions explained why basal metabolic rate remained unchanged. Conclusion/interpretation. Improved glycaemia promotes weight gain by decreasing both basal metabolic rate and glucosuria. Use of metformin decreases weight gain by reducing energy intake and is therefore a useful adjunct to insulin therapy in patients with Type II diabetes. [Diabetologia (1999)

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Section: Discussionsupporting

confidence: 86%

Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus

1999

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“…The fact that metformin did not reduce BP in our sample agrees with other studies (10,22,23,25), although there are reports of SBP and DBP reduction with this drug (26,27). A possible explanation for this discrepancy may be the fact that not all patients who lose weight experience reductions in their plasma renin and aldosterone levels (28,29).…”

Section: Other Parameterssupporting

confidence: 84%

Effects of metformin on the glycemic control, lipid profile, and arterial blood pressure of type 2 diabetic patients with metabolic syndrome already on insulin

Júnior

Sá

Guedes

et al. 2006

Braz J Med Biol Res

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Fifty-seven type 2 diabetic patients with metabolic syndrome and on insulin were assessed by a paired analysis before and 6 months after addition of metformin as combination therapy to evaluate the impact of the association on glycemic control, blood pressure, and lipid profile. This was a historical cohort study in which the files of type 2 diabetic patients with metabolic syndrome on insulin were reviewed. The body mass index (BMI), waist circumference, lipid profile, A1C level, fasting blood glucose level, daily dose of NPH insulin, systolic blood pressure, and diastolic blood pressure were assessed in each patient before the start of metformin and 6 months after the initiation of combination therapy. Glycemic control significantly improved (P < 0.001) after the addition of metformin (1404.4 ± 565.5 mg/day), with 14% of the 57 patients reaching A1C levels up to 7%, and 53% reaching values up to 8%. There was a statistically significant reduction (P < 0.05) of total cholesterol (229.0 ± 29.5 to 214.2 ± 25.0 mg/ dL), BMI (30.7 ± 5.4 to 29.0 ± 4.0 kg/m 2 ), waist circumference (124.6 ± 11.7 to 117.3 ± 9.3 cm), and daily necessity of insulin. The reduction of total cholesterol occurred independently of the reductions of A1C (9.65 ± 1.03 to 8.18 ± 1.01%) and BMI and the reduction of BMI and WC did not interfere with the improvement of A1C. In conclusion, our study showed the efficacy of the administration of metformin and insulin simultaneously without negative effects. No changes were detected in HDL-cholesterol or blood pressure.

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“…It improves glycemic control by enhancing insulin sensitivity in the liver (leading to a decrease in basal hepatic glucose production) and muscle (leading to an increase in glucose uptake) (6). In insulin-treated type 2 diabetic patients, the use of metformin improves insulin sensitivity and glycemic control, leading to a reduction in the daily insulin requirement (IR) (7)(8)(9). In type 1 diabetes, addition of metformin to insulin therapy has been assessed in a few trials involving few patients or in uncontrolled studies of short duration (10 -12).…”

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confidence: 99%

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

et al. 2002

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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.

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Metformin for obese, insulin-treated diabetic patients: improvement in glycaemic control and reduction of metabolic risk factors

Cited by 159 publications

References 26 publications

Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus

Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus

Effects of metformin on the glycemic control, lipid profile, and arterial blood pressure of type 2 diabetic patients with metabolic syndrome already on insulin

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

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