[Effectiveness of treatment with metformin in patients with type 2 diabetes mellitus poorly controlled with insulin treatment]. Metformin as additional therapy in adolescents with poorly controlled type 1 diabetes: randomised placebo-controlled trial with aspects on insulin sensitivity. [The combination of insulin and metformin in obese patients with type-2 diabetes mellitus]. Metformin for obese, insulin-treated diabetic patients: improvement in glycaemic control and reduction of metabolic risk factors. Use of multisystemic therapy to improve regimen adherence among adolescents with type 1 diabetes in chronic poor metabolic control: a randomized controlled trial. Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. Combination of insulin and metformin in the treatment of type 2 diabetes. A retrospective chart review of uncontrolled use of metformin as an add-on therapy in type 2 diabetes. Improved treatment satisfaction but no difference in metabolic control when using continuous subcutaneous insulin infusion vs. multiple daily injections in children at onset of type 1 diabetes mellitus.
Combined treatment with insulin plus metformin could be a good alternative to improve the glycemic control in patients with type 2 diabetes mellitus poorly controlled with insulin therapy. We retrospectively studied 21 obese insulin-treated type 2 diabetic patients with deficient metabolic control (HbA1c 9.2 +/- 1.2%) who were treated with metformin for a minimum of 8 months. After 4 months of treatment, a significant decrease in the percentage of HbA1c was observed (delta HbA1c -1.07 +/- 1.12%; p < 0.01), with maintained values since then. Non changes in body weight or insulin requirement were noted. Our results suggest that the addition of metformin to insulin treatment is a safe and effective strategy for the improvement of glycemic control among obese type 2 diabetic patients. Metabolic control often deteriorates during puberty in children with type 1 diabetes. The aim of the present study was to investigate whether addition of metformin for 3 Months improves metabolic control and insulin sensitivity.
                Twenty-six of 30 randomised adolescents with type 1 diabetes (18 females, eight males) completed a double-blind placebo-controlled trial. Their mean age was 16.9+/-1.6 (s.d.) Years, mean glycated haemoglobin (HbA(1c)) 9.5+/-1.1% and daily insulin dosage 1.2+/-0.3 U/kg. The participants were randomised to receive oral metformin or placebo for 3 Months. HbA(1c) was measured Monthly, and peripheral insulin sensitivity was assessed by a euglycaemic hyperinsulinaemic clamp at baseline and at the end of the study.
                HbA(1c) decreased significantly in the group treated with metformin, from 9.6 to 8.7% (P<0.05), but was unchanged in the placebo group (9.5 vs 9.2%). Peripheral glucose uptake divided by mean plasma insulin concentration was increased in the metformin group (P<0.05) but not in the placebo group. Initial insulin sensitivity was inversely correlated to changes in HbA(1c) (r=-0.62; P<0.05) and positively correlated to changes in insulin sensitivity (r=0.77; P<0.01).
                In this double-blind placebo-controlled study we found that metformin improves metabolic control in adolescents with type 1 diabetes. The effect seems to be associated with an increased insulin-induced glucose uptake. Principal: to show that the addition of metformin to insulin treatment in type-2 DM obese patients with poor metabolic control (HbA1c > 7.5%) causes a 50% increase after one year in the number of patients with acceptable (HbA1c < or = 7.5%) or good (HbA1c < 6.5%) control, and to determine how many patients reduced their HbA1c by a point. Secondary: to determine the relationship between the BMI at the start of treatment and the difference between HbA1c values before and after treatment.
                Quasi-experimental before-and-after intervention study.
                Diabetes clinic at the San Carlos Hospital, consisting of patients referred from primary care.
                31 obese people with type-2 DM and with poor metabolic control (HbA1c > 7.5%) in spite of insulin treatment were chosen by consecutive sampling as they attended for consultation. Three people left due to their intolerance of metformin.
                Metformin was added progressively over a year in total doses of 1.7 mg. All those parameters considered in diabetes control were measured, the main criterion of evaluation being the HbA1c figures.
                Patients with poor metabolic control changed from 100% at the start of the study to 42.9% after a year (p = 0.0000). There was a 1.75% mean reduction of HbA1c. 78.57% of patients reduced their HbA1c by a point. The relationship between the BMI before the start of treatment and the HbA1c difference at the start and end gave a Pearson's correlation coefficient of r = -0.39 (p = 0.04).
                Adding metformin to the treatment of obese type-2 DM patients with poor metabolic control and on insulin treatment improved their control. The efficacy and safety of metformin in the treatment of obese, non-insulin-dependent, diabetic subjects poorly controlled by insulin after secondary failure to respond to sulphonylureas has been investigated. Fifty insulin-treated, obese diabetics participated in this prospective, randomised double-blind six-month trial. After a four-week run-in period, during which all patients were given placebo (single-blind), patients were randomly assigned to continue to receive placebo or to active treatment with metformin. At six months, there was a relevant and significant improvement in glycaemic control in diabetics receiving the combined insulin-metformin treatment (decrease in glucose -4.1 mmol.l-1; glycosylated haemoglobin A1 decrease -1.84%). No significant changes were seen in diabetics receiving insulin and placebo. There was a significant decrease in blood lipids (trygliceride and cholesterol), an increase in HDL-cholesterol and a reduction in blood pressure in diabetics taking metformin. These positive findings were most marked in the 14 diabetics who experienced a good response to metformin (glucose profile < 10 mmol.l-1), and were less marked but still significant in the remaining 13 diabetics, whose response to therapy was not so good (glucose profile > 10 mmol.l-1). The fasting insulin level was significantly lower after six months of combined insulin-metformin treatment as shown by a 25% reduction in the daily dose of insulin (-21.6 U/day). Metformin was well tolerated by all diabetics.(ABSTRACT TRUNCATED AT 250 WORDS) The aim of this study was to determine whether multisystemic therapy (MST), an intensive, home-based psychotherapy, could improve adherence and metabolic control and decrease rates of hospital utilization among adolescents with chronically poorly controlled type 1 diabetes.
                A randomized controlled trial was conducted with 127 adolescents with type 1 diabetes and chronically poor metabolic control (HbA(1c) [A1C] > or =8% for the past year) who received their diabetes care in a children's hospital located in a major Midwestern city. Participants randomly assigned to MST received treatment for approximately 6 months. Data were collected at baseline and at 7 months posttest (i.e., treatment termination). Changes in A1C adherence, as measured by semistructured interviews and blood glucose meters and hospital admissions and emergency department visits, were assessed.
                In intent-to-treat analyses, participation in MST was associated with significant improvements in the frequency of blood glucose testing as assessed by blood glucose meter readings (F[1,125] = 16.75, P = 0.001) and 24-h recall interviews (F[1,125] = 6.70, P = 0.011). Participants in MST also had a decreasing number of inpatient admissions, whereas the number of inpatient admissions increased for control subjects (F[1,125] = 6.25, P = 0.014). Per protocol analyses replicated intent-to-treat analyses but also showed a significant improvement in metabolic control for adolescents receiving MST compared with control subjects (F[1,114] = 4.03, P = 0.047).
                Intensive, home-based psychotherapy improves the frequency of blood glucose testing and metabolic control and decreases inpatient admissions among adolescents with chronically poorly controlled type 1 diabetes. Metformin therapy for adults and children with type 2 diabetes is well established. However, its role in the treatment of insulin resistance and obesity in children and adolescents is less clearly defined.
                We assessed the effect of metformin on body composition and insulin sensitivity in pediatric subjects with exogenous obesity.
                Patients referred to a pediatric endocrine clinic were enrolled in a randomized, double-blind, crossover trial.
                Twenty-eight patients (13 males) aged 9-18 yr participated in the study.
                Patients received metformin (1 g twice daily) and placebo for 6 months, each with a 2-wk washout period.
                Body composition (anthropometry, dual-energy x-ray absorptiometry, and abdominal magnetic resonance imaging), and insulin sensitivity (Si; minimal model, fasting insulin and glucose) were measured at baseline and 6 and 12 months.
                Mean age of subjects at baseline was 12.5 +/- 2.2 yr, median body mass index z-score 2.54 (range, 1.93-2.85). Metformin had a greater treatment effect over placebo for weight (-4.35 kg, P = 0.02), body mass index (-1.26 kg/m(2), P = 0.002), waist circumference (-2.8 cm, P = 0.003), sc abdominal adipose tissue (-52.5 cm(2), P = 0.002), and fasting insulin (-2.2 mU/liter, P = 0.011). Si improved in 45% of subjects while on metformin and 27% of subjects while on placebo (P = 0.21).
                Metformin therapy for obese insulin-resistant pediatric patients results in significant improvement in body composition and fasting insulin. Although improvement in Si was noted in many individuals, Si was a less useful parameter for analysis of group data, possibly because of effects of variable compliance and changing Si during puberty. To investigate the metabolic effects of metformin, as compared with placebo, in type 2 diabetic patients intensively treated with insulin.
                Metformin improves glycemic control in poorly controlled type 2 diabetic patients. Its effect in type 2 diabetic patients who are intensively treated with insulin has not been studied. A total of 390 patients whose type 2 diabetes was controlled with insulin therapy completed a randomized controlled double-blind trial with a planned interim analysis after 16 weeks of treatment. The subjects were selected from three outpatient clinics in regional hospitals and were randomly assigned to either the placebo or metformin group, in addition to insulin therapy. Intensive glucose monitoring with immediate insulin adjustments according to strict guidelines was conducted. Indexes of glycemic control, insulin requirements, body weight, blood pressure, plasma lipids, hypoglycemic events, and other adverse events were measured.
                Of the 390 subjects, 37 dropped out (12 in the placebo and 25 in the metformin group). Of those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with improved glycemic control (mean daily glucose at 16 weeks 7.8 vs. 8.8 mmol/l, P = 0.006; mean GHb 6.9 vs. 7.6%, P < 0.0001); reduced insulin requirements (63.8 vs. 71.3 IU, P < 0.0001); reduced weight gain (-0.4 vs. +1.2 kg, P < 0.01); and decreased plasma LDL cholesterol (-0.21 vs. -0.02 mmol/l, P < 0.01). Risk of hypoglycemia was similar in both groups. CONCLUSIONS-In type 2 diabetic patients who are intensively treated with insulin, the combination of insulin and metformin results in superior glycemic control compared with insulin therapy alone, while insulin requirements and weight gain are less. The hyperglycemia, hyperinsulinemia, insulin resistance, and obesity syndrome associated with type 2 diabetes can have debilitating consequences. The biguanide metformin has a mechanism of action that is complementary to those of insulin and the sulfonylureas, suggesting that combination therapy that includes metformin may result in improved glycemic control. The purpose of this retrospective chart review was to determine the effects of adding metformin in an uncontrolled fashion to existing therapy in obese patients with type 2 diabetes who had suboptimal glycemic control and insulin resistance. For the review, the records of 124 patients were divided into two groups: group 1 included 71 patients who were taking insulin with or without a sulfonylurea, and group 2 consisted of 53 patients who were taking a sulfonylurea alone. Metformin was added to patients' existing therapy in conjunction with downward titration of the sulfonylurea and insulin doses. A retrospective chart review was conducted at the end of 6 months for group 1 and at the end of 12 months for group 2 to determine the change from baseline in measures of diabetes control (ie, insulin and sulfonylurea dose, glycated hemoglobin [Hb A1c] value, body mass index [BMI], and lipid profiles). In group 1, the mean insulin dose decreased from 46.4 U/d at baseline to 6.1 U/d at the end of follow-up. Eighty-three percent of the patients were able to discontinue insulin therapy completely. Similarly, group 2 had statistically significant reductions in mean sulfonylurea dose. Both groups also achieved statistically significant reductions in Hb A1c, BMI, and total cholesterol level. The addition of metformin to treatment with insulin or sulfonylureas, either alone or in combination, significantly improved glycemic control and cholesterol levels and promoted weight loss in obese type 2 diabetic patients with insulin resistance. Less than 5% of patients reported mild, transient gastrointestinal side effects, none of which required cessation of metformin therapy. Five patients discontinued metformin due to lack of efficacy. The aim of this study was to compare safety, metabolic control, and treatment satisfaction in children/adolescents at onset of type 1 diabetes mellitus who were treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI).
                Seventy-two children/adolescents (7-17 yr of age) were enrolled in this open, randomized, parallel, multicenter study. Approximately half of the patients were treated with MDI (natural protamine hagedorn [NPH] insulin twice daily and rapid-acting insulin three to -four times daily, n = 38) by pen, and the other half received CSII (n = 34). The patients were followed for 24 months with clinical visits at the entry of the study and after 1, 6, 12, and 24 months. During these visits, hemoglobin A1c, insulin doses, weight, and height were registered. Severe episodes of hypoglycemia and ketoacidosis as well as technical problems were recorded. In addition, the patients/parents answered the Diabetes Treatment Satisfaction Questionnaire.
                There was no significant difference in metabolic control between the treatment groups. Treatment satisfaction was significantly higher in the group treated with CSII compared with the MDI group (p <or= 0.01 at all screening visits). There were no episodes of ketoacidosis and there was no significant difference regarding severe hypoglycemia between the treatment groups.
                CSII treatment proved to be a safe therapy in children/adolescents followed for 24 months after onset of their diabetes. Treatment satisfaction was higher in the CSII group, although there was no difference in metabolic control compared with the MDI group.
There is some evidence suggesting improvement of metabolic control in poorly controlled adolescents with type 1 diabetes, on addition of metformin to insulin therapy. Stronger evidence is required from larger studies, carried out over longer time periods to document the long-term effects on metabolic control, health-related quality of life as well as morbidity and mortality in those patients.