Dataset Information

Effect and Safety of Adding Metformin to Insulin Therapy in Treating Adolescents With Type 1 Diabetes Mellitus: An Updated Meta-Analysis of 10 Randomized Controlled Trials.

ABSTRACT:

Background

The role of metformin in the treatment of adolescents with type 1 diabetes mellitus (T1DM) remains controversial. We conducted this updated meta-analysis to generate a comprehensive assessment regarding the effect and safety of metformin in treating adolescents with T1DM.

Methods

We systematically searched PubMed, Embase, and the Cochrane Central Registry of Controlled Trials (CENTRAL) from their inception to November 2021 to identify randomized controlled trials evaluating the efficacy of metformin in the treatment of adolescents with T1DM. The primary outcome was the HbA1c level, and secondary outcomes included the body mass index (BMI), total insulin daily dose (TIDD) (unit/kg/d), hypoglycemia events, diabetes ketoacidosis (DKA) events, and gastrointestinal adverse events (GIAEs). Statistical analysis was conducted using RevMan 5.4 and STATA 14.0.

Results

Ten studies enrolling 539 T1DM adolescents were included. Results suggested that metformin significantly decreased the HbA1c level at 12 months (mean difference [MD])=-0.50, 95% confidence interval [CI]=-0.61 to -0.39, P < 0.01); BMI (kg/m²) at 3 months (MD=-1.05, 95%CI=-2.05 to -0.05, P=0.04); BMI z-score at 6 months (MD=-0.10, 95%CI=-0.14 to -0.06, P<0.01); and TIDD at 3 (MD=-0.13, 95%CI=-0.20 to -0.06, P<0.01), 6 (MD=-0.18, 95%CI=-0.25 to -0.11, P<0.01), and 12 (MD=-0.42, 95%CI=-0.49 to -0.35, P<0.01) months but significantly increased the risk of hypoglycemia events (risk ratio [RR]=3.13, 95%CI=1.05 to 9.32, P=0.04) and GIAEs (RR=1.64, 95%CI=1.28 to 2.10, P<0.01). For remaining outcomes at other time points, no statistical difference was identified. Sensitivity analysis confirmed the robustness of all pooled results.

Conclusions

The use of metformin might result in decreased BMI (kg/m²), BMI z-score, and TIDD and increased risk of hypoglycemia events and GIAEs in adolescents with T1DM. However, future studies are required to further confirm the optimal dose and duration of metformin therapy.

SUBMITTER: Liu Y

PROVIDER: S-EPMC9190285 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Effect and Safety of Adding Metformin to Insulin Therapy in Treating Adolescents With Type 1 Diabetes Mellitus: An Updated Meta-Analysis of 10 Randomized Controlled Trials.

Liu Ying Y Chen Hongbo H Li Hui H Li Liman L Wu Jin J Li Hong H

Frontiers in endocrinology 20220530

<h4>Background</h4>The role of metformin in the treatment of adolescents with type 1 diabetes mellitus (T1DM) remains controversial. We conducted this updated meta-analysis to generate a comprehensive assessment regarding the effect and safety of metformin in treating adolescents with T1DM.<h4>Methods</h4>We systematically searched PubMed, Embase, and the Cochrane Central Registry of Controlled Trials (CENTRAL) from their inception to November 2021 to identify randomized controlled trials evalua ...[more]

PMID: 35707462

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Project description:BackgroundThe safety and efficacy of different drugs in treatment of gestational diabetes mellitus (GDM) patients who could not maintain normal glucose level only through diet and exercise remains to be debated. We performed this network meta-analysis (NAM) to compare and rank different antidiabetic drugs in glucose level control and pregnancy outcomes in GDM patients.MethodsWe searched PubMed, Cochrane Library, Web of Science, and Embase up to December 31, 2016. Randomized controlled trials (RCTs) related to different drugs in the treatment of GDM patients were enrolled. We extracted the relevant information and assessed the risk of bias with the Cochrane risk of bias tool. We did pair-wise meta-analyses using the fixed-effects model or random-effects model and then adopted random-effects NAM combining both direct and indirect evidence within a Bayesian framework, to calculate the odds ratio (OR) or standardized mean difference (SMD) and to draw a surface under the cumulative ranking curve of the neonatal and maternal outcomes of different treatments in GDM patients.ResultsThirty-two randomized controlled trials (RCTs) were included in this NAM, including 6 kinds of treatments (metformin, metformin plus insulin, insulin, glyburide, acarbose, and placebo). The results of the NAM showed that regarding the incidence of macrosomia and LGA, metformin had lower incidence than glyburide (OR, 0.5411 and 0.4177). In terms of the incidence of admission to the NICU, insulin had higher incidence compared with glyburide (OR, 1.844). As for the incidence of neonatal hypoglycemia, metformin had lower incidence than insulin and glyburide (OR, 0.6331 and 0.3898), and insulin was lower than glyburide (OR, 0.6236). For mean birth weight, metformin plus insulin was lower than insulin (SMD, -0.5806), glyburide (SMD, -0.7388), and placebo (SMD, -0.6649). Besides, metformin was observed to have lower birth weight than glyburide (SMD, 0.2591). As for weight gain, metformin and metformin plus insulin were lower than insulin (SMD, -0.9166, -1.53). Ranking results showed that glyburide might be the optimum treatment regarding average glucose control, and metformin is the fastest in glucose control for GDM patients; glyburide have the highest incidence of macrosomia, preeclampsia, hyperbilirubinemia, neonatal hypoglycemia, shortest gestational age at delivery, and lowest mean birth weight; metformin (plus insulin when required) have the lowest incidence of macrosomia, PIH, LGA, RDS, low gestational age at delivery, and low birth weight. Besides, insulin had the highest incidence of NICU admission, acarbose had the lowest risk of neonatal hypoglycemia.ConclusionOur study concluded that metformin is fastest in glucose control, with a more favorable pregnancy outcomes-would be a better option, but its rate of glucose control is the lowest.However, glyburide is the optimumtreatment regarding the rate of glucose control, but withmore adverse outcomes. This NAMbased on 32 RCTs will strongly help to guide further development of management for GDM patients, clinicians should carefully balance the risk-benefit profile of different treatments according to various situations.

Project description:ObjectiveTo assess the effect of metformin versus placebo both in combination with insulin analogue treatment on changes in carotid intima-media thickness (IMT) in patients with type 2 diabetes.Design and settingInvestigator-initiated, randomised, placebo-controlled trial with a 2 × 3 factorial design conducted at eight hospitals in Denmark.Participants and interventions412 participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥ 7.5% (≥ 58 mmol/mol); body mass index >25 kg/m2) were in addition to open-labelled insulin treatment randomly assigned 1:1 to 18 months blinded metformin (1 g twice daily) versus placebo, aiming at an HbA1c ≤ 7.0% (≤ 53 mmol/mol).OutcomesThe primary outcome was change in the mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight and hypoglycaemic and serious adverse events were other prespecified outcomes.ResultsChange in the mean carotid IMT did not differ significantly between the groups (between-group difference 0.012 mm (95% CI -0.003 to 0.026), p=0.11). HbA1c was more reduced in the metformin group (between-group difference -0.42% (95% CI -0.62% to -0.23%), p<0.001)), despite the significantly lower insulin dose at end of trial in the metformin group (1.04 IU/kg (95% CI 0.94 to 1.15)) compared with placebo (1.36 IU/kg (95% CI 1.23 to 1.51), p<0.001). The metformin group gained less weight (between-group difference -2.6 kg (95% CI -3.3 to -1.8), p<0.001). The groups did not differ with regard to number of patients with severe or non-severe hypoglycaemic or other serious adverse events, but the metformin group had more non-severe hypoglycaemic episodes (4347 vs 3161, p<0.001).ConclusionsMetformin in combination with insulin did not reduce carotid IMT despite larger reduction in HbA1c, less weight gain, and smaller insulin dose compared with placebo plus insulin. However, the trial only reached 46% of the planned sample size and lack of power may therefore have affected our results.Trial registration numberNCT00657943; Results.

Dataset Information

Effect and Safety of Adding Metformin to Insulin Therapy in Treating Adolescents With Type 1 Diabetes Mellitus: An Updated Meta-Analysis of 10 Randomized Controlled Trials.

Background

Methods

Results

Conclusions

Publications

Effect and Safety of Adding Metformin to Insulin Therapy in Treating Adolescents With Type 1 Diabetes Mellitus: An Updated Meta-Analysis of 10 Randomized Controlled Trials.

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