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American Journal of Therapeutics 2020Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later. But...
BACKGROUND
Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later. But even with the availability of oral glucose-lowering drugs, insulin supplementation was often needed to achieve good glucose control in type 2 diabetes. Insulin NPH became the basal insulin therapy of choice and adding NPH to metformin and/or sulfonylureas became the standard of care until basal insulin analogs were developed and new glucose-lowering drugs became available.
AREAS OF UNCERTAINTY
The advantages in cost-benefit of insulin analogs and their combination with new glucose-lowering drugs are still a matter of debate. There is no general agreement on how to avoid inertia by prescribing insulin therapy in type 2 diabetes when really needed, as reflected by the diversity of recommendations in the current clinical practice guidelines.
DATA SOURCES
When necessary for this review, a systematic search of the evidence was done in PubMed and Cochrane databases.
THERAPEUTIC ADVANCES
Adding new oral glucose-lowering drugs to insulin such as DPP-4 inhibitors lead to a modest HbA1c reduction without weight gain and no increase in hypoglycemia. When SGLT-2 inhibitors are added instead, there is a slightly higher HbA1c reduction, but with body weight and blood pressure reduction. The downside is the increase in genital tract infections. GLP-1 receptor agonists have become the best alternative when basal insulin fails, particularly using fixed ratio combinations. Rapid-acting insulins via the inhaled route may also become an alternative for insulin supplementation and/or intensification. "Smart insulins" are under investigation and may become available for clinical use in the near future.
CONCLUSIONS
Aggressive weight loss strategies together with the new glucose-lowering drugs which do not cause hypoglycemia nor weight gain should limit the number of patients with type 2 diabetes needing insulin. Nevertheless, because of therapeutic inertia and the progressive nature of the disease, many need at least a basal insulin supplementation and insulin analogs are the best choice as they become more affordable. Fixed ratio combinations with GLP1 receptor agonists are a good choice for intensification of insulin therapy.
Topics: Administration, Oral; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 31567175
DOI: 10.1097/MJT.0000000000001088 -
Journal of Diabetes Feb 2023Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID-19.
METHODS
We searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID-19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non-English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission.
RESULTS
The use of metformin rather than other glucose-lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p < .001). Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p < .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p < .02). There was a statistically significant decrease in hospitalization for SGLT-2i users vs nonusers (RR: 0.89, 95% CI: 0.84-0.95, p < .001). Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p < 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p < .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p = .04).
CONCLUSIONS
AGM use was not associated with increased mortality. However, metformin and GLP-1RA use reduced mortality risk statistically significantly. DPP-4i use was associated with a statistically significant increase in the risk of hospitalization and admission to the ICU.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; COVID-19; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Glucagon-Like Peptide-1 Receptor
PubMed: 36690377
DOI: 10.1111/1753-0407.13359 -
Diabetes Research and Clinical Practice Feb 2021This systematic review and meta-analysis aims to evaluate the safety and efficacy of the newer glucose lowering treatments on glycemic control, weight, blood pressure... (Meta-Analysis)
Meta-Analysis
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 Hb (%) (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 Hb (%) (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 Hb (%) (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.
Topics: Administration, Oral; Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Humans; Hypoglycemia; Hypoglycemic Agents; Islam
PubMed: 33271228
DOI: 10.1016/j.diabres.2020.108562 -
Diabetes Research and Clinical Practice Feb 2021We aimed to conduct a systematic review and meta-analysis regarding the use of incretin-based therapies including dipeptidyl peptidase-4 (DPP-4) inhibitors and... (Meta-Analysis)
Meta-Analysis
AIMS
We aimed to conduct a systematic review and meta-analysis regarding the use of incretin-based therapies including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists as well as sodium-glucose co-transporter-2 (SGLT2) inhibitorsin persons with posttransplantation diabetes mellitus (PTDM) so as to assess both their efficacy and safety.
METHODS
We searched for publications on Kidney/Renal Transplantation and DPP-4 inhibitors, GLP-1-receptor agonists and SGLT-2 inhibitors and included every study using these antidiabetics. A p-value < 0.05 was considered statistical significant.
RESULTS
Sixteen studies and 310 individuals with a mean age of 55.98 ± 8.81 years were included in the analysis. Participants received DPP-4 inhibitors in 8 studies, SGLT-2 inhibitors in 6 studies and GLP-1 receptor agonists in 2 studies, with a mean follow-up of 22.03 ± 14.95 weeks. Hemoglobin A1c (HbA1c) reduction was demonstrated in 10 studies (mean +/- standard deviation (MD) = - 0.38%, I = 45%). MD of HbA1c was -0.3741 and -0.4596 mg/dl for DPP-4 inhibitors and SGLT-2 inhibitors respectively. Nine studies demonstrated differences in fasting plasma glucose (FPG) (MD = - 25,76) and 5 studies in post-prandial glucose (PPG) (MD = - 6.61) before and following treatment. Most studies did not show adverse effects on the glomerular filtration rate (GFR) and hepatic function.
CONCLUSIONS
DPP-4 inhibitors and SGLT2 inhibitors appear both efficacious and safe in renal transplant recipients. More high-quality studies are required to guide therapeutic choices for PTDM.
Topics: Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Incretins; Kidney Function Tests; Kidney Transplantation; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33338553
DOI: 10.1016/j.diabres.2020.108604 -
Journal of Diabetes Research 2020Sub-Saharan Africa (SSA) is observing an accelerating prevalence rate of type 2 diabetes mellitus (T2DM) influenced by gene-environment interaction of modifiable and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Sub-Saharan Africa (SSA) is observing an accelerating prevalence rate of type 2 diabetes mellitus (T2DM) influenced by gene-environment interaction of modifiable and nonmodifiable factors. We conducted a systematic review and meta-analysis on the heritability and genetic risk of T2DM in SSA.
METHODS
We reviewed all published articles on T2DM in SSA between January 2000 and December 2019 and available in PubMed, Scopus, and Web of Science. Studies that reported on the genetics and/or heritability of T2DM or indicators of glycaemia were included. Data extracted included the study design, records of family history, pattern and characteristics of inheritance, genetic determinants, and effects estimates.
RESULTS
The pattern and characteristics of T2DM heritability in SSA are preference for maternal aggregation, higher among first degree compared to second-degree relatives; early age-onset (<50 years), and inherited abnormalities of beta-cell function/mass. The overall prevalence of T2DM was 28.2% for the population with a positive family history (PFH) and 11.2% for the population with negative family history (NFH). The pooled odds ratio of the impact of PFH on T2DM was 3.29 (95% CI: 2.40-4.52). Overall, 28 polymorphisms in 17 genes have been investigated in relation with T2DM in SSA. Almost all studies used the candidate gene approach with most (45.8%) of genetic studies published between 2011 and 2015. Polymorphisms in , , , , , , and were found to be associated with T2DM, with overlapping effect on specific cardiometabolic traits. Genome-wide studies identified ancestry-specific signals (, , and ) and as the only transferable genetic risk variants to SSA population. polymorphism was investigated in multiple studies with consistent effects and low-moderate statistical heterogeneity. Effect sizes were modestly strong [odds ratio = 6.17 (95% CI: 2.03-18.81), codominant model; 2.27 (95% CI: 1.50-3.44), additive model; 1.75 (95% CI: 1.18-2.59), recessive model]. Current evidence on the heritability and genetic markers of T2DM in SSA populations is limited and largely insufficient to reliably inform the genetic architecture of T2DM across SSA regions.
Topics: Adiponectin; Africa South of the Sahara; Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Haptoglobins; Humans; Phosphoric Diester Hydrolases; Polymorphism, Single Nucleotide; Potassium Channels, Inwardly Rectifying; Pyrophosphatases; Sulfonylurea Receptors; Transcription Factor 7-Like 2 Protein; Tumor Necrosis Factor-alpha
PubMed: 32685554
DOI: 10.1155/2020/3198671 -
Frontiers in Endocrinology 2024The benefit of first-line use of sodium-dependent glucose transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes... (Meta-Analysis)
Meta-Analysis
First-line treatment with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in type 2 diabetic population at low risk of cardiovascular disease: a meta-analysis.
BACKGROUND
The benefit of first-line use of sodium-dependent glucose transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes mellitus (T2DM) with low risk of cardiovascular diseases are not clear.
METHODS
PubMed, EMBASE and Cochrane Library databases were searched to identify eligible randomized controlled trials. We used the odds ratio (OR) and mean difference (MD) and the corresponding 95% confidence interval (CI) to assess the dichotomous and continuous variable, respectively.
RESULTS
Thirteen studies involving 2,885 T2DM at low risk of cardiovascular diseases were included. Compared to placebo, first line use of SGLT2i significantly reduced glycosylated hemoglobin type A1C (HbA1c) (MD: -0.72), weight (MD: -1.32) and fasting plasma glucose (FPG) (MD: -27.05) levels. Compared with metformin, SGLT2i reduced body weight (MD: -1.50) and FPG (MD: -10.13) more effectively, with similar reduction for HbA1c (MD: -0.05). No significant increased safety adverse was found for SGLT2i, including nasopharyngitis (OR: 1.07), urinary tract infection (OR: 2.31), diarrhea (OR: 1.18) and hypoglycemia (OR: 1.06). GLP-1RAs significantly reduced HbA1c (MD: -1.13), weight (MD: -2.12) and FPG (MD: -31.44) levels as first-line therapy compared to placebo. GLP-1RAs significantly increased occurrence of diarrhea (OR: 2.18), hypoglycemia (OR: 3.10), vomiting (OR: 8.22), and nausea (OR: 4.41).
CONCLUSION
First line use of SGLT2i and GLP-1RAs is effective in reducing HbA1c, weight, and FPG levels in T2DM patients at low risk for cardiovascular disease. SGLT2i may be superior to metformin in controlling body weight and FPG. GLP-1RAs may increase the occurrence of diarrhea, hypoglycemia, vomiting, and nausea.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (International Prospective Register of Systematic Reviews. https://www.york.ac.uk/inst/crd, CRD42022347233).
Topics: Humans; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diarrhea; Glucagon-Like Peptide-1 Receptor Agonists; Glycated Hemoglobin; Hypoglycemia; Hypoglycemic Agents; Metformin; Nausea; Sodium; Systematic Reviews as Topic; Vomiting
PubMed: 38348420
DOI: 10.3389/fendo.2024.1289643 -
Journal of Alzheimer's Disease Reports 2024Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in...
BACKGROUND
Alzheimer's disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in targeting core AD pathology, clinical studies are limited.
OBJECTIVE
A systematic review was performed to evaluate GLP-1 RAs in AD for their potential to target core AD pathology and improve cognition.
METHODS
Searches were conducted via three different databases (PubMed, Embase, and Cochrane Library). Search terms included Medical Subject Headings (MeSH) terms: 'glucagon-like peptide 1 receptor agonist' and 'Alzheimer's disease', as well as entry terms 'GLP-1 RA', 'AD', and three types of GLP-1 RA: 'liraglutide', 'exenatide', and 'lixisenatide'.
RESULTS
A total of 1,444 studies were screened. Six articles that met criteria were included (four randomized control trials [RCTs] and two protocol studies). Two RCTs with amyloid-β and tau biomarker endpoints did not observe an end of treatment difference between the placebo and treated groups. In three RCTs with cognitive endpoints, there was no end of treatment difference between placebo and treated groups. GLP-1 RA showed metabolic benefits, such as lower body mass index and improved glucose levels on oral glucose tolerance tests in treated groups. GLP-1 RA may mitigate the decline in cerebral glucose metabolism and show enhanced blood-brain glucose transport capacity using F-FDG PET, however, more data is needed.
CONCLUSIONS
GLP-1 RA therapy did not alter amyloid-β and tau biomarkers nor show improvements in cognition but showed potential metabolic and neuroprotective benefits.
PubMed: 38746639
DOI: 10.3233/ADR-230181 -
Pharmacological Research Mar 2021Formulation of insulin analogs and its delivery are developed in over recent years but glycemic control in most patients with type-1 diabetes mellitus (DM) is not... (Meta-Analysis)
Meta-Analysis Review
Formulation of insulin analogs and its delivery are developed in over recent years but glycemic control in most patients with type-1 diabetes mellitus (DM) is not adequate yet. The aim of this meta-analysis is to evaluate the efficacy of dapagliflozin in patients with type-1 DM. The MEDLINE/PubMed, Scopus, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched up to Aug 2020 to identify the potential literature. Random-effects model (DerSimonian and Laird method) was used to estimate the pooled effect size as weighted mean difference (WMD) with 95 % confidence interval (CI). Five randomized placebo-controlled trials with 11 arms were included in the quantitative analysis. The pooled results suggested a significant reduction in glycated hemoglobin A1C (HbA1C; WMD: -0.36 %, 95 % CI: -0.55, -0.18), body weight (WMD: -4.02 kg, 95 % CI: -4.78, -3.25), and total daily insulin dose (TDID; WMD: -10.36 %, 95 % CI: -13.42, -7.29), as well as an increase in 24-h urinary glucose excretion (24-h UGE; WMD: 90.02 g/24-h, 95 % CI: 72.96, 107.09) in dapagliflozin group compared to control group. Dose of dapagliflozin had a significant effect on body weight reduction (Coef = -3.7, p = 0.01) and 24-h UGE (coef = 0.85, p = 0.005). Pooled results of this meta-analysis identified a significant reduction in HbA1c levels, body weight, and TDID, and a substantial increase in 24-h UGE in patients who received dapagliflozin versus placebo.
Topics: Animals; Benzhydryl Compounds; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Glucosides; Glycated Hemoglobin; Humans; Insulin; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome
PubMed: 33515709
DOI: 10.1016/j.phrs.2021.105456 -
The Cochrane Database of Systematic... Jul 2023Fasting during Ramadan is obligatory for adult Muslims, except those who have a medical illness. Many Muslims with type 2 diabetes (T2DM) choose to fast, which may... (Review)
Review
BACKGROUND
Fasting during Ramadan is obligatory for adult Muslims, except those who have a medical illness. Many Muslims with type 2 diabetes (T2DM) choose to fast, which may increase their risks of hypoglycaemia and dehydration.
OBJECTIVES
To assess the effects of interventions for people with type 2 diabetes fasting during Ramadan.
SEARCH METHODS
We searched CENTRAL, MEDLINE, PsycINFO, CINAHL, WHO ICTRP and ClinicalTrials.gov (29 June 2022) without language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) conducted during Ramadan that evaluated all pharmacological or behavioural interventions in Muslims with T2DM.
DATA COLLECTION AND ANALYSIS
Two authors screened and selected records, assessed risk of bias and extracted data independently. Discrepancies were resolved by a third author. For meta-analyses we used a random-effects model, with risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes with their associated 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach.
MAIN RESULTS
We included 17 RCTs with 5359 participants, with a four-week study duration and at least four weeks of follow-up. All studies had at least one high-risk domain in the risk of bias assessment. Four trials compared dipeptidyl-peptidase-4 (DPP-4) inhibitors with sulphonylurea. DPP-4 inhibitors may reduce hypoglycaemia compared to sulphonylureas (85/1237 versus 165/1258, RR 0.53, 95% CI 0.41 to 0.68; low-certainty evidence). Serious hypoglycaemia was similar between groups (no events were reported in two trials; 6/279 in the DPP-4 versus 4/278 in the sulphonylurea group was reported in one trial, RR 1.49, 95% CI 0.43 to 5.24; very low-certainty evidence). The evidence was very uncertain about the effects of DPP-4 inhibitors on adverse events other than hypoglycaemia (141/1207 versus 157/1219, RR 0.90, 95% CI 0.52 to 1.54) and HbA1c changes (MD -0.11%, 95% CI -0.57 to 0.36) (very low-certainty evidence for both outcomes). No deaths were reported (moderate-certainty evidence). Health-related quality of life (HRQoL) and treatment satisfaction were not evaluated. Two trials compared meglitinides with sulphonylurea. The evidence is very uncertain about the effect on hypoglycaemia (14/133 versus 21/140, RR 0.72, 95% CI 0.40 to 1.28) and HbA1c changes (MD 0.38%, 95% CI 0.35% to 0.41%) (very low-certainty evidence for both outcomes). Death, serious hypoglycaemic events, adverse events, treatment satisfaction and HRQoL were not evaluated. One trial compared sodium-glucose co-transporter-2 (SGLT-2) inhibitors with sulphonylurea. SGLT-2 may reduce hypoglycaemia compared to sulphonylurea (4/58 versus 13/52, RR 0.28, 95% CI 0.10 to 0.79; low-certainty evidence). The evidence was very uncertain for serious hypoglycaemia (one event reported in both groups, RR 0.90, 95% CI 0.06 to 13.97) and adverse events other than hypoglycaemia (20/58 versus 18/52, RR 1.00, 95% CI 0.60 to 1.67) (very low-certainty evidence for both outcomes). SGLT-2 inhibitors result in little or no difference in HbA1c (MD 0.27%, 95% CI -0.04 to 0.58; 1 trial, 110 participants; low-certainty evidence). Death, treatment satisfaction and HRQoL were not evaluated. Three trials compared glucagon-like peptide 1 (GLP-1) analogues with sulphonylurea. GLP-1 analogues may reduce hypoglycaemia compared to sulphonylurea (20/291 versus 48/305, RR 0.45, 95% CI 0.28 to 0.74; low-certainty evidence). The evidence was very uncertain for serious hypoglycaemia (0/91 versus 1/91, RR 0.33, 95% CI 0.01 to 7.99; very low-certainty evidence). The evidence suggests that GLP-1 analogues result in little to no difference in adverse events other than hypoglycaemia (78/244 versus 55/255, RR 1.50, 95% CI 0.86 to 2.61; very low-certainty evidence), treatment satisfaction (MD -0.18, 95% CI -3.18 to 2.82; very low-certainty evidence) or change in HbA1c (MD -0.04%, 95% CI -0.45% to 0.36%; 2 trials, 246 participants; low-certainty evidence). Death and HRQoL were not evaluated. Two trials compared insulin analogues with biphasic insulin. The evidence was very uncertain about the effects of insulin analogues on hypoglycaemia (47/256 versus 81/244, RR 0.43, 95% CI 0.13 to 1.40) and serious hypoglycaemia (4/131 versus 3/132, RR 1.34, 95% CI 0.31 to 5.89) (very low-certainty evidence for both outcomes). The evidence was very uncertain for the effect of insulin analogues on adverse effects other than hypoglycaemia (109/256 versus 114/244, RR 0.83, 95% CI 0.44 to 1.56; very low-certainty evidence), all-cause mortality (1/131 versus 0/132, RR 3.02, 95% CI 0.12 to 73.53; very low-certainty evidence) and HbA1c changes (MD 0.03%, 95% CI -0.17% to 0.23%; 1 trial, 245 participants; very low-certainty evidence). Treatment satisfaction and HRQoL were not evaluated. Two trials compared telemedicine with usual care. The evidence was very uncertain about the effect of telemedicine on hypoglycaemia compared with usual care (9/63 versus 23/58, RR 0.42, 95% CI 0.24 to 0.74; very low-certainty evidence), HRQoL (MD 0.06, 95% CI -0.03 to 0.15; very low-certainty evidence) and HbA1c change (MD -0.84%, 95% CI -1.51% to -0.17%; very low-certainty evidence). Death, serious hypoglycaemia, AEs other than hypoglycaemia and treatment satisfaction were not evaluated. Two trials compared Ramadan-focused patient education with usual care. The evidence was very uncertain about the effect of Ramadan-focused patient education on hypoglycaemia (49/213 versus 42/209, RR 1.17, 95% CI 0.82 to 1.66; very low-certainty evidence) and HbA1c change (MD -0.40%, 95% CI -0.73% to -0.06%; very low-certainty evidence). Death, serious hypoglycaemia, adverse events other than hypoglycaemia, treatment satisfaction and HRQoL were not evaluated. One trial compared drug dosage reduction with usual care. The evidence is very uncertain about the effect of drug dosage reduction on hypoglycaemia (19/452 versus 52/226, RR 0.18, 95% CI 0.11 to 0.30; very low-certainty evidence). No participants experienced adverse events other than hypoglycaemia during the study (very low-certainty evidence). Death, serious hypoglycaemia, treatment satisfaction, HbA1c change and HRQoL were not evaluated.
AUTHORS' CONCLUSIONS
There is no clear evidence of the benefits or harms of interventions for individuals with T2DM who fast during Ramadan. All results should be interpreted with caution due to concerns about risk of bias, imprecision and inconsistency between studies, which give rise to low- to very low-certainty evidence. Major outcomes, such as mortality, health-related quality of life and severe hypoglycaemia, were rarely evaluated. Sufficiently powered studies that examine the effects of various interventions on these outcomes are needed.
Topics: Adult; Humans; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Hypoglycemia; Insulin; Fasting
PubMed: 37435938
DOI: 10.1002/14651858.CD013178.pub2 -
Endocrine Feb 2020To evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of combinations of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of type 2 diabetes or obese adults: a systematic review and meta-analysis.
PURPOSE
To evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM) or obese adults.
METHODS
A meta-analysis was conducted of trials by searching in PubMed, Embase, CENTRAL, Web of Science, and Scopus.
RESULTS
A total of five randomized controlled trials (RCTs) and six nonrandomized controlled trials (NCTs) enrolled 1604 participants were identified for meta-analysis. Compared with control/placebo, the combination therapy group had significantly reduced fasting plasma glucose level and 2 h postprandial glucose by 1.28 mmol/L (95% confidence interval [CI]: -1.39, -1.16; p < 0.001) and 1.34 mmol/L (95% CI: -1.47, -1.21; p < 0.001); glycosylated hemoglobin (HbA1c) by 1.32% (95% CI: -1.43, -1.20; p < 0.001); body weight by 0.93 kg (95% CI: -1.04, -0.83; p < 0.001), and systolic blood pressure (SBP) by 1.05 mmHg (95% CI: -1.17, -0.93; p < 0.001). The incidence of genital mycotic infections and urinary infections did not significantly differ from those in the control group, with relative risks (RRs) of 1.67 (95% CI: 0.85, 3.27; p = 0.651) and 1.25 (95% CI: 0.73, 2.15; p = 0.905), respectively. A decreased incidence of cardiovascular events was seen in the combination therapy group (RR = 0.19; 95% CI: 0.04, 0.96; p = 0.403), while an incidence of hypoglycemia was reported (RR = 2.22; 95% CI: 1.20, 4.10; p = 0.71).
CONCLUSIONS
SGLT2 inhibitors and GLP-1 agonists combination treatment improved glycemic control, reduced body weight, and decreased SBP without an increase in total adverse events or genital and urinary infections in patients with T2DM or obesity.
Topics: Adult; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Obesity; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 31900793
DOI: 10.1007/s12020-019-02175-6