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Efficacy and safety of the newer oral hypoglycemic agents in patients with T2DM during Ramadan: A systematic review and meta-analysis.
Gad, H, Hayat, T, Al-Muhannadi, H, Malik, BR, Mussleman, P, Malik, RA
Diabetes research and clinical practice. 2021;:108562
Abstract
AIMS: This systematic review and meta-analysis aims to evaluate the safety and efficacy of the newer glucose lowering treatments on glycemic control, weight, blood pressure and hypoglycemia in patients with T2DM during Ramadan. METHODS A literature search was done in PubMed, Embase, and the Cochrane Library. Quality assessment was done using the ROBINS-I and Cochrane tools for risk of bias and analyses were performed using RevMan version 5.3. RESULTS A total of 20 studies were included in the meta-analysis. Dipeptidyl peptidase-4 inhibitors (DPP-4i) led to a significant reduction in HbA1c (%) (SMD -0.25) and a non-significant decrease in weight (kg) (SMD -1.06) during Ramadan. Glucagon-like peptide (GLP-1) agonist therapy was associated with a significant decrease in HbA1c (%) (SMD -0.68) and a non-significant decrease in weight (kg) (SMD -2.57) and systolic blood pressure (SBP) (mmHg) (SMD -3.50) after Ramadan. Sodium-glucose co-transporter 2 inhibitor (SGLT-2i) therapy was associated with a significant decrease in HbA1c (%) (SMD -0.51) and a non-significant decrease in weight (kg) (SMD -1.41), SBP (SMD -1.10) and diastolic blood pressure (DBP) (mmHg) (SMD -2.08) after Ramadan. CONCLUSIONS This systematic review and meta-analysis shows clinical benefits with the newer glucose lowering medications in patients with T2DM who fast during Ramadan.
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A Model-Based Meta-Analysis of 24 Antihyperglycemic Drugs for Type 2 Diabetes: Comparison of Treatment Effects at Therapeutic Doses.
Maloney, A, Rosenstock, J, Fonseca, V
Clinical pharmacology and therapeutics. 2019;(5):1213-1223
Abstract
Model-based meta-analysis was used to compare glycemic control, weight changes, and hypoglycemia risk across 24 antihyperglycemic drugs used to treat type 2 diabetes. Electronic searches identified 229 randomized controlled studies comprising 121,914 patients. To ensure fair and unbiased treatment comparisons, the analyses adjusted for important differences between studies, including duration of treatment, baseline glycated hemoglobin, and drug dosages. At the approved doses, glycemic control was typically greatest with glucagon-like peptide 1 receptor agonists (GLP-1RAs), and least with dipeptidyl peptidase-4 (DPP-4) inhibitors. Weight loss was highly variable across GLP-1RAs but was similar across sodium-glucose cotransporter 2 (SGLT2) inhibitors. Large weight increases were observed with sulfonylureas and thiazolidinediones. Hypoglycemia risk was highest with sulfonylureas, although gliclazide was notably lower. Hypoglycemia risk for DPP-4 inhibitors, SGLT2 inhibitors, and thiazolidinediones was generally very low but increased slightly for both GLP-1RAs and metformin. In summary, important differences between and within drug classes were identified.
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Safety of Ramadan fasting in young patients with type 1 diabetes: A systematic review and meta-analysis.
Loh, HH, Lim, LL, Loh, HS, Yee, A
Journal of diabetes investigation. 2019;(6):1490-1501
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AIMS/INTRODUCTION Although patients with type 1 diabetes are medically exempt, many insist on fasting during Ramadan. Multiple daily insulin injections (MDI), premixed insulin and continuous subcutaneous insulin infusion (CSII) are commonly used. To date, little is known about the safety of Ramadan fasting in these patients. MATERIALS AND METHODS We pooled data from 17 observational studies involving 1,699 patients treated with either CSII or non-CSII (including premixed and MDI) regimen. The study outcomes were the frequencies of hypoglycemia, hyperglycemia and/or ketosis. Given the lack of patient-level data, separate analyses for premixed and MDI regimen were not carried out. RESULTS The CSII-treated group (n = 203) was older (22.9 ± 6.9 vs 17.8 ± 4.0 years), and had longer diabetes duration (116.7 ± 66.5 vs 74.8 ± 59.2 months) and lower glycated hemoglobin (7.8 ± 1.1% vs 9.1 ± 2.0%) at baseline than the non-CSII-treated group (n = 1,496). The non-CSII-treated group had less non-severe hypoglycemia than the CSII-treated group (22%, 95% CI 13-34 vs 35%, 95% CI 17-55). Of the non-CSII-treated group, 7.1% (95% CI 5.8-8.5) developed severe hypoglycemia, but none from the CSII-treated group did. The non-CSII-treated group was more likely to develop hyperglycemia (12%, 95% CI 3-25 vs 8.8%, 95% CI 0-31) and ketosis (2.5%, 95% CI 1.0-4.6 vs 1.6%, 95% CI 0.1-4.7), and discontinue fasting (55%, 95% CI 34-76 vs 31%, 95% CI 9-60) than the CSII-treated group. CONCLUSIONS The CSII regimen had lower rates of severe hypoglycemia and hyperglycemia/ketosis, but a higher rate of non-severe hyperglycemia than premixed/MDI regimens. These suggest that appropriate patient selection with regular, supervised fine-tuning of the basal insulin rate with intensive glucose monitoring might mitigate the residual hypoglycemia risk during Ramadan.
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Efficacy and safety of dual SGLT 1/2 inhibitor sotagliflozin in type 1 diabetes: meta-analysis of randomised controlled trials.
Musso, G, Gambino, R, Cassader, M, Paschetta, E
BMJ (Clinical research ed.). 2019;:l1328
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OBJECTIVE To assess the efficacy and safety of dual sodium glucose cotransporter (SGLT) 1/2 inhibitor sotagliflozin in type 1 diabetes mellitus. DESIGN Meta-analysis of randomised controlled trials. DATA SOURCES Medline; Cochrane Library; Embase; international meeting abstracts; international and national clinical trial registries; and websites of US, European, and Japanese regulatory authorities, up to 10 January 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials evaluating the effect of sotagliflozin versus active comparators or placebo on glycaemic and non-glycaemic outcomes and on adverse events in type 1 diabetes in participants older than 18. Three reviewers extracted data for study characteristics, outcomes of interest, and risk of bias and summarised strength of evidence using the grading of recommendations assessment, development, and evaluation approach. Main outcomes were pooled using random effects models. RESULTS Of 739 records identified, six randomised placebo controlled trials (n=3238, duration 4-52 weeks) were included. Sotagliflozin reduced levels of glycated haemoglobin (HbA1c; weighted mean difference -0.34% (95% confidence interval -0.41% to -0.27%), P<0.001); fasting plasma glucose (-16.98 mg/dL, -22.1 to -11.9; 1 mg/dL=0.0555 mmol/L) and two hour-postprandial plasma glucose (-39.2 mg/dL, -50.4 to -28.1); and daily total, basal, and bolus insulin dose (-8.99%, -10.93% to -7.05%; -8.03%, -10.14% to -5.93%; -9.14%, -12.17% to -6.12%; respectively). Sotagliflozin improved time in range (weighted mean difference 9.73%, 6.66% to 12.81%) and other continuous glucose monitoring parameters, and reduced body weight (-3.54%, -3.98% to -3.09%), systolic blood pressure (-3.85 mm Hg, -4.76 to -2.93), and albuminuria (albumin:creatinine ratio -14.57 mg/g, -26.87 to -2.28). Sotagliflozin reduced hypoglycaemia (weighted mean difference -9.09 events per patient year, -13.82 to -4.36) and severe hypoglycaemia (relative risk 0.69, 0.49 to 0.98). However, the drug increased the risk of ketoacidosis (relative risk 3.93, 1.94 to 7.96), genital tract infections (3.12, 2.14 to 4.54), diarrhoea (1.50, 1.08 to 2.10), and volume depletion events (2.19, 1.10 to 4.36). Initial HbA1c and basal insulin dose adjustment were associated with the risk of diabetic ketoacidosis. A sotagliflozin dose of 400 mg/day was associated with a greater improvement in most glycaemic and non-glycaemic outcomes than the 200 mg/day dose, without increasing the risk of adverse events. The quality of evidence was high to moderate for most outcomes, but low for major adverse cardiovascular events and all cause death. The relatively short duration of trials prevented assessment of long term outcomes. CONCLUSIONS In type 1 diabetes, sotagliflozin improves glycaemic and non-glycaemic outcomes and reduces hypoglycaemia rate and severe hypoglycaemia. The risk of diabetic ketoacidosis could be minimised by appropriate patient selection and down-titration of the basal insulin dose.
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Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.
Mazidi, M, Karimi, E, Rezaie, P, Ferns, GA
Journal of diabetes and its complications. 2017;(7):1237-1242
Abstract
AIM: To undertake a systematic review and meta-analysis of randomized controlled trials of the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) therapy on serum C-reactive protein (CRP) concentrations. METHOD PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched for the period up until March 16, 2016. Prospective studies evaluating the impact of GLP-1 RAs on serum CRP were identified. A random effects model (using the DerSimonian-Laird method) and generic inverse variance methods were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Heterogeneity was quantitatively assessed using the I2 index. Random effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of potential moderator. International Prospective Register for Systematic Reviews (PROSPERO) number CRD42016036868. RESULTS Meta-analysis of the data from 7 treatment arms revealed a significant reduction in serum CRP concentrations following treatment with GLP-1 RAs (WMD -2.14 (mg/dL), 95% CI -3.51, -0.78, P=0.002; I2 96.1%). Removal of one study in the meta-analysis did not change the result in the sensitivity analysis (WMD -2.14 (mg/dL), 95% CI -3.51, -0.78, P=0.002; I2 96.1%), indicating that our results could not be solely attributed to the effect of a single study. Random effects meta-regression was performed to evaluate the impact of potential moderator on the estimated effect size. Changes in serum CRP concentration were associated with the duration of treatment (slope -0.097, 95% CI -0.158, -0.042, P<0.001). CONCLUSIONS This meta-analysis suggests that GLP-1 RAs therapy causes a significant reduction in CRP.
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The effect of vitamin D supplementation on glucose metabolism in type 2 diabetes mellitus: A systematic review and meta-analysis of intervention studies.
Lee, CJ, Iyer, G, Liu, Y, Kalyani, RR, Bamba, N, Ligon, CB, Varma, S, Mathioudakis, N
Journal of diabetes and its complications. 2017;(7):1115-1126
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AIMS: We aimed to assess whether vitamin D supplementation improves glucose metabolism in adults with type 2 diabetes. METHODS PubMed and Cochrane database were searched up to July 1st 2016 for randomized controlled trials that assessed the relationship between vitamin D supplementation and glucose metabolism (change in hemoglobin A1C (HbA1C) and fasting blood glucose (FBG)) among adults with type 2 diabetes. RESULTS Twenty nine trials (3324 participants) were included in the systematic review. Among 22 studies included in the meta-analysis, 19 reported HbA1C, 16 reported FBG outcomes and 15 were deemed poor quality. There was a modest reduction in HbA1C (-0.32% [-0.53 to -0.10], I2=91.9%) compared to placebo after vitamin D supplementation but no effect on FBG (-2.33mg/dl [-6.62 to 1.95], I2=59.2%). In studies achieving repletion of vitamin D deficiency (n=7), there were greater mean reductions in HbA1C (-0.45%, [-1.09 to 0.20]) and FBG (-7.64mg/dl [-16.25 to 0.97]) although not significant. CONCLUSIONS We found a modest reduction of HbA1C after vitamin D treatment in adults with type 2 diabetes albeit with substantial heterogeneity between studies and no difference in FBG. Larger studies are needed to further evaluate the glycemic effects of vitamin D treatment especially in patients with vitamin D deficiency.
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Dietary sugars versus glucose tablets for first-aid treatment of symptomatic hypoglycaemia in awake patients with diabetes: a systematic review and meta-analysis.
Carlson, JN, Schunder-Tatzber, S, Neilson, CJ, Hood, N
Emergency medicine journal : EMJ. 2017;(2):100-106
Abstract
BACKGROUND While glucose tablets have been advocated for treating symptomatic hypoglycaemia in awake patients, dietary sugars may be more convenient. We performed a systematic review to compare the impact of these treatment options on the relief of symptomatic hypoglycaemia, time to resolution of symptoms, blood glucose levels, complications and hospital length of stay. METHOD We searched PubMed, Embase and the Cochrane Library through 28 June 2016 and assessed the quality of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach. Reference lists from a subset of the resulting articles were mined for additional, potentially eligible papers. We calculated the risk ratio (RR) of each treatment option for the preselected outcomes of interest. RESULTS Of the 1774 identified papers, four studies met the inclusion criteria; three randomised controlled trials totalling 502 hypoglycaemic events treated with dietary sugars and 223 with glucose tablets and one observational study with 13 events treated with dietary sugars and 9 with glucose tablets. The dietary forms of sugar included sucrose, fructose, orange juice, jelly beans, Mentos, cornstarch hydrolysate, Skittles and milk. In the pooled analysis, patients treated with dietary sugars had a lower resolution of symptoms 15 min after treatment compared with glucose tablets (RR 0.89, 95% CI 0.83 to 0.95). CONCLUSIONS When compared with dietary sugars, glucose tablets result in a higher rate of relief of symptomatic hypoglycaemia 15 min after ingestion and should be considered first, if available, when treating symptomatic hypoglycaemia in awake patients.
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Psyllium fiber improves glycemic control proportional to loss of glycemic control: a meta-analysis of data in euglycemic subjects, patients at risk of type 2 diabetes mellitus, and patients being treated for type 2 diabetes mellitus.
Gibb, RD, McRorie, JW, Russell, DA, Hasselblad, V, D'Alessio, DA
The American journal of clinical nutrition. 2015;(6):1604-14
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BACKGROUND A number of health benefits are associated with intake of soluble, viscous, gel-forming fibers, including reduced serum cholesterol and the attenuation of postprandial glucose excursions. OBJECTIVE We assess the effects of psyllium, which is a soluble, gel-forming, nonfermented fiber supplement, on glycemic control in patients who were being treated for type 2 diabetes mellitus (T2DM) and in patients who were at risk of developing T2DM. DESIGN A comprehensive search was performed of available published literature (Scopus scientific database) and clinical records stored by Procter & Gamble with the use of key search terms to identify clinical studies that assessed the glycemic effects of psyllium in nondiabetic, pre-T2DM, and T2DM patients. RESULTS We identified 35 randomized, controlled, clinical studies that spanned 3 decades and 3 continents. These data were assessed in 8 meta-analyses. In patients with T2DM, multiweek studies (psyllium dosed before meals) showed significant improvement in both the fasting blood glucose (FBG) concentration (-37.0 mg/dL; P < 0.001) and glycated hemoglobin (HbA1c) [-0.97% (-10.6 mmol/mol); P = 0.048]. Glycemic effects were proportional to baseline FBG; no significant glucose lowering was observed in euglycemic subjects, a modest improvement was observed in subjects with pre-T2DM, and the greatest improvement was observed in subjects who were being treated for T2DM. CONCLUSIONS These data indicate that psyllium would be an effective addition to a lifestyle-intervention program. The degree of psyllium's glycemic benefit was commensurate with the loss of glycemic control. Because the greatest effect was seen in patients who were being treated for T2DM, additional studies are needed to determine how best to incorporate psyllium into existing prevention and treatment algorithms with concomitant hypoglycemic medications.
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Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: A meta-analysis of seven clinical trials.
Russell-Jones, D, Gall, MA, Niemeyer, M, Diamant, M, Del Prato, S
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2015;(10):898-905
Abstract
BACKGROUND AND AIMS Basal insulin analogues have a reduced risk of hypoglycaemia compared with NPH insulin, but hypoglycaemia still remains a major impediment to achieving recommended fasting plasma glucose (FPG) targets in patients with diabetes. Insulin degludec (IDeg) is a new basal insulin that forms soluble multihexamers after subcutaneous injection resulting in an ultra-long duration of action and stable glucose-lowering effect. The aim of this analysis was to compare the effect of IDeg on FPG and nocturnal confirmed hypoglycaemia as compared to insulin glargine (IGlar). METHODS AND RESULTS Data were included from seven phase 3a, randomised, open-label, treat-to-target clinical trials in which once-daily IDeg was compared with once-daily IGlar. Two trials included a total of 957 patients with type 1 diabetes (T1D) and five trials included a total of 3360 patients with type 2 diabetes (T2D); all trials were 26 or 52 weeks in duration. Confirmed hypoglycaemia was defined as plasma glucose <3.1 mmol/L or severe episodes requiring assistance, and nocturnal hypoglycaemia occurred between 00:01 and 05:59. In all trials, the mean end-of-trial FPG was lower for IDeg than IGlar, reaching statistical significance in three trials. Similarly, IDeg was associated with a lower rate of nocturnal confirmed hypoglycaemia vs. IGlar, which was statistically significant in three trials, regardless of type of diabetes or background therapy. CONCLUSION This analysis shows that the lower rate of nocturnal confirmed hypoglycaemia seen with IDeg relative to IGlar is accompanied by a reduced mean FPG, in particular in patients with T2D.
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Physical activity interventions in children and young people with Type 1 diabetes mellitus: a systematic review with meta-analysis.
Quirk, H, Blake, H, Tennyson, R, Randell, TL, Glazebrook, C
Diabetic medicine : a journal of the British Diabetic Association. 2014;(10):1163-73
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AIMS: To synthesize evidence from randomized and non-randomized studies of physical activity interventions in children and young people with Type 1 diabetes so as to explore clinically relevant health outcomes and inform the promotion of physical activity. METHOD We conducted a search of CINAHL Plus, the Cochrane Library, EMBASE, MEDLINE, PsycINFO, SCOPUS, SportDiscus and Web of Science between October and December 2012. Eligible articles included subjects aged ≤18 years with Type 1 diabetes and a physical activity intervention that was more than a one-off activity session. Physiological, psychological, behavioural or social outcomes were those of interest. RESULTS A total of 26 articles (10 randomized and 16 non-randomized studies), published in the period 1964-2012, were reviewed. Although there was heterogeneity in study design, methods and reporting, 23 articles reported at least one significant beneficial health outcome at follow-up. Meta-analyses of these studies showed potential benefits of physical activity on HbA1c (11 studies, 345 participants, standardized mean difference -0.52, 95% CI -0.97 to -0.07; P = 0.02), BMI (four studies, 195 participants, standardized mean difference -0.41, 95% CI -0.70 to -0.12; P = 0.006) and triglycerides (five studies, 206 participants, standardized mean difference -0.70, 95% CI -1.25 to -0.14; P = 0.01).The largest effect size was for total cholesterol (five studies, 206 participants, standardized mean difference -0.91, 95% CI -1.66 to -0.17; P = 0.02). CONCLUSIONS Physical activity is important for diabetes management and has the potential to delay cardiovascular disease, but there is a lack of studies that are underpinned by psychological behaviour change theory, promoting sustained physical activity and exploring psychological outcomes. There remains a lack of knowledge of how to promote physical activity in people with Type 1 diabetes.