Effect of metformin on the high‐density lipoprotein proteome in youth with type 1 diabetes

Gourgari, Evgenia; Nadeau, Kristen J.; Pyle, Laura; Playford, Martin P.; Ma, Junfeng; Mehta, Nehal N.; Remaley, Alan T.; Gordon, Scott M.

doi:10.1002/edm2.261

Cited by 5 publications

(9 citation statements)

References 41 publications

(78 reference statements)

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“…After checking the titles and abstracts of the remaining studies, 14 studies were retrieved. After evaluating the full text, 10 studies met our selection criteria and were included in the final analysis ( 16 – 19 , 31 – 36 ). The PRISMA flowchart for literature retrieval and selection is displayed in Figure 1 .…”

Section: Resultsmentioning

confidence: 99%

“…The sample size of each study ranged from 24 to 140, with a total number of 539. Four studies ( 18 , 19 , 33 , 35 ) enrolled overweight/obese adolescents, and the remaining studies ( 16 , 17 , 31 , 32 , 34 , 36 ) included general adolescents. The daily dose of metformin was different among studies, ranging from 500 to 2,000 mg.…”

Section: Resultsmentioning

confidence: 99%

“…Treatment duration varied from 3 to 12 months. All studies ( 16 – 19 , 31 – 36 ) reported the baseline HbA1c level and total insulin daily dose, seven studies ( 17 , 19 , 31 , 32 , 34 – 36 ) reported BMI as kilogram per square meter, and five studies ( 16 , 18 , 19 , 33 , 34 ) reported BMI as z-score. The baseline data of these indicators is shown in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

“…Overall, one study ( 17 ) was judged to be at low overall RoB, three studies ( 16 , 34 , 35 ) were judged to be at moderate overall RoB, and six studies ( 18 , 19 , 31 – 33 , 36 ) were judged to be at high RoB. Of these ten studies, nine studies ( 16 – 19 , 31 – 35 ) appropriately generated a random sequence but only four studies ( 17 , 18 , 32 , 35 ) clearly reported the methods of performing allocation concealment. All studies blinded personnel, participants, and the outcome assessor.…”

Section: Resultsmentioning

confidence: 99%

“…Unfortunately, definitive results were not achieved by them. Moreover, since the publication of two previous meta-analyses, several potentially eligible randomized controlled trials (RCTs) have also been published ( 16 – 19 ). It is necessary to combine all available studies to produce more reliable results for resolving controversial results.…”

Section: Introductionmentioning

confidence: 99%

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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

Chen

et al. 2022

Front. Endocrinol.

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BackgroundThe 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.MethodsWe 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.ResultsTen 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.ConclusionsThe 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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Chen

et al. 2022

Front. Endocrinol.

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Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes

Wang,

Hou

et al. 2024

Sci Rep

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Chiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist, which passed phase III clinical trials and was newly approved in China for use as an adjunct to diet and exercise in glycemic control in adult patients with Type 2 Diabetes (T2D). To explore the circulating protein signatures associated with the administration of chiglitazar in T2D patients, we conducted a comparative longitudinal study using plasma proteome profiling. Of the 157 T2D patients included in the study, we administered chiglitazar to a specific group, while the controls were given either placebo or sitagliptin. The plasma proteomes were profiled at baseline and 12 and 24 weeks post-treatment using data-independent acquisition mass spectrometry (DIA-MS). Our study indicated that 13 proteins were associated with chiglitazar treatment in T2D patients, including 10 up-regulated proteins (SHBG, TF, APOA2, APOD, GSN, MBL2, CFD, PGLYRP2, A2M, and APOA1) and 3 down-regulated proteins (PRG4, FETUB, and C2) after treatment, which were implicated in the regulation of insulin sensitivity, lipid metabolism, and inflammation response. Our study provides insight into the response of chiglitazar treatment from a proteome perspective and demonstrates the multi-faceted effects of chiglitazar in T2D patients, which will help the clinical application of chiglitazar and further study of its action mechanism.

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Effect of metformin adjunct therapy on cardiometabolic parameters in Indian adolescents with type 1 diabetes: a randomized controlled trial

Mondkar,

Khandagale,

Shah

et al. 2024

Front. Clin. Diabetes Healthc.

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IntroductionInsulin resistance is being increasingly reported in type-1 Diabetes (T1D) and is known to accelerate microvascular complications. The Asian Indian population has a higher risk of double diabetes development compared to Caucasians. Hence, we studied the effect of adding Metformin to standard insulin therapy on glycemic control, insulin sensitivity (IS), cardiometabolic parameters and body composition in Indian adolescents with T1D.MethodsA Randomized controlled trial was conducted spanning 9 months (Registration number:CTRI/2019/11/022126). Inclusion: Age 10-19 years, T1D duration>1year, HbA1c>8% Exclusion: Uncontrolled vascular complications/comorbidities, Metformin intolerance, concomitant drugs affecting insulin sensitivity. Participants were randomized to Metformin/Placebo (n=41 each) groups and age, sex, duration-matched. Assessments were performed at baseline, 3 and 9 months.Results82 participants aged 14.7 ± 3years (40 females) were enrolled, with a mean diabetes duration of 5.2 ± 2.3 years. Over 9 months, HbA1c decreased significantly by 0.8 (95% confidence interval: -1.2 to -0.3) from 9.8 ± 1.8% to 9.1 ± 1.7% on Metformin but remained largely unchanged (difference of 0.2, 95% confidence interval: -0.7 to 0.2) i.e. 9.9 ± 1.6% and 9.7 ± 2.2% on placebo. HbA1c improvement correlated negatively with baseline IS (EGDR:r= -0.3;SEARCH:r = -0.24, p<0.05) implying better HbA1c-lowering in those with decreased initial IS. CGM-based glycemic variability (standard deviation) reduced by 6.3 mg/dL (95% confidence interval: -12.9 to 0.2) from 100.2 ± 19.1 mg/dL to 93.7 ± 19.9 mg/dL in those on Metformin (p=0.05) but not placebo (94.0 ± 20.5; 90.0 ± 22.6 mg/dL). Insulin sensitivity: CACTIexa & SEARCH scores demonstrated no change with Metformin but significant worsening on placebo. Significant increase in LDL-C(42%), total cholesterol(133.6 to 151.1 mg/dL), triglyceride (60.0 to 88.0 mg/dL) and carotid intima-media thickness was noted on placebo but not Metformin. Weight, BMI, fat Z-scores increased significantly on placebo but not Metformin. Adverse events (AE) were minor; AE, compliance and safety parameters were similar between the two groups.ConclusionMetformin as an adjunct to insulin in Asian Indian adolescents with T1D demonstrated beneficial effect on glycemic control, glycemic variability, IS, lipid profile, vascular function, weight and body fat, with a good safety profile when administered for 9 months.

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Effect of metformin on the high‐density lipoprotein proteome in youth with type 1 diabetes

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 5 publications

References 41 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

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

Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes

Effect of metformin adjunct therapy on cardiometabolic parameters in Indian adolescents with type 1 diabetes: a randomized controlled trial

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