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Combination therapy with GLP-1 receptor agonists and basal insulin: a systematic review of the literature.

ABSTRACT: Treatment algorithms for type 2 diabetes call for intensification of therapy over time as the disease progresses and glycaemic control worsens. If diet, exercise and oral antihyperglycaemic medications (OAMs) fail to maintain glycaemic control then basal insulin is added and ultimately prandial insulin may be required. However, such an intensification strategy carries risk of increased hypoglycaemia and weight gain, both of which are associated with worse long-term outcomes. An alternative strategy is to intensify therapy by the addition of a short-acting glucagon-like peptide-1 receptor agonist (GLP-1?RA) rather than prandial insulin. Short-acting GLP-1?RAs such as exenatide twice daily are particularly effective at reducing postprandial glucose while basal insulin has a greater effect on fasting glucose, providing a physiological rationale for this complementary approach. This review analyzes the latest randomized controlled clinical trials of insulin/GLP-1?RA combination therapy and examines results from 'real-world' use of the combinations as reported through observational and clinical practice studies. The most common finding across all types of studies was that combination therapy improved glycaemic control without weight gain or an increased risk of hypoglycaemia. Many studies reported weight loss and a reduction in insulin use when a GLP-1?RA was added to existing insulin therapy. Overall, the relative degree of benefit to glycaemic control and weight was influenced by the insulin titration employed in conjunction with the GLP-1?RA. The greatest glycaemic benefits were observed in studies with structured titration of insulin to glycaemic targets while the greatest weight benefits were observed in studies with a protocol-specified focus on insulin sparing. The adverse event profile of GLP-1?RAs in the reviewed trials was similar to that reported with GLP-1?RAs as monotherapy or in combination with OAMs with gastrointestinal events being the most commonly reported.

SUBMITTER: Balena R

PROVIDER: S-EPMC3662998 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Combination therapy with GLP-1 receptor agonists and basal insulin: a systematic review of the literature.

Balena R R Hensley I E IE Miller S S Barnett A H AH

Diabetes, obesity & metabolism 20121112 6

Treatment algorithms for type 2 diabetes call for intensification of therapy over time as the disease progresses and glycaemic control worsens. If diet, exercise and oral antihyperglycaemic medications (OAMs) fail to maintain glycaemic control then basal insulin is added and ultimately prandial insulin may be required. However, such an intensification strategy carries risk of increased hypoglycaemia and weight gain, both of which are associated with worse long-term outcomes. An alternative strat ...[more]

PMID: 23061470

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Project description:IntroductionOnce-weekly semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that is currently available as 1.0 mg and 0.5 mg dose for the treatment of type 2 diabetes (T2D). Currently, no head-to-head trial investigating once-weekly semaglutide as an add-on to basal insulin vs other GLP-1 receptor agonists (GLP-1 RAs) is available. The aim of this study was to conduct a network meta-analysis (NMA) to assess the efficacy and safety of once-weekly semaglutide vs other GLP-1 RAs in patients with T2D inadequately controlled on basal insulin.MethodsA systematic literature review was performed to identify all trials of GLP-1 RAs as an add-on to basal insulin in patients with T2D. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in an NMA), including the change from baseline in glycated hemoglobin (HbA1c), body weight, and systolic blood pressure, and the incidence of nausea, vomiting, and diarrhea. Data were synthesized using a NMA and a Bayesian framework.ResultsIn total, eight studies were included across the base-case analyses. The results demonstrate that once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA1c (- 0.88% to - 1.39% vs comparators) and weight (- 1.49 to - 4.69 kg vs comparators) and similar odds of experiencing nausea, vomiting, or diarrhea vs all GLP-1 RA comparators. Once-weekly semaglutide 1.0 mg was also equally effective at reducing systolic blood pressure compared with liraglutide 1.8 mg. Once-weekly semaglutide 0.5 mg significantly reduced HbA1c vs the majority of other GLP-1 RAs, except liraglutide 1.8 mg QD. The odds of experiencing nausea were significantly lower with once-weekly semaglutide 0.5 mg compared with all GLP-1 RA comparators.ConclusionOnce-weekly semaglutide 1.0 mg as an add-on to basal insulin is likely to be the most efficacious GLP-1 RA for reducing HbA1c and weight from baseline after 6 months of treatment. The efficacy of once-weekly semaglutide is not associated with a significant increase in the incidence of gastrointestinal side-effects vs other GLP-1 RAs.FundingNovo Nordisk.

Project description:ObjectivesBoth glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metformin (MET) have markedly antiobesity effects in overweight/obese polycystic ovary syndrome (PCOS) patients. However, there was no literature to compare the antiobesity effects of these two medicines. Therefore, a systematic review and meta-analysis were conducted in our present study to evaluate the antiobesity effects of GLP-1RAs either as monotherapy or combined with MET in comparison with MET alone in overweight/obese PCOS patients.MethodsAll randomized controlled trials (RCTs) which reported the efficacy of GLP-1RAs and MET in overweight/obese PCOS patients in Medline (from Pubmed), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were independently searched by two reviewers. The random-effect model was used to pool data extracted from the included literature. The weighted mean difference (WMD) and 95% confidence interval (CI) were used to present the meta-analysis results (PROSPERO registration number: CRD42020173199).ResultsA total of eight eligible RCTs were finally enrolled in our meta-analysis from the 587 retrieved literature. The results showed that GLP-1RAs alone or combined with MET was associated with a greater weight loss (N?=?318, WMD?=?-2.61, 95% CI: -3.51 to -1.72, P ? 0.001, I 2?=?77.5%), more obvious reduction of waist circumference (N?=?276, WMD?=?-3.46, 95% CI: -4.36 to -2.56, P ? 0.001, I 2?=?0.0%), and body mass index (BMI) (N?=?318, WMD?=?-0.93, 95% CI: -1.60 to -0.26, P=0.007, I 2?=?84.9%) in overweight/obese PCOS patients when compared with MET alone. Further sensitivity analysis demonstrated that the meta-analysis results of the efficacy differences in terms of body weight, waist circumference, and BMI were relatively stable and reliable.ConclusionOur meta-analysis demonstrated that the antiobesity effect of GLP-1RAs alone or combined with MET? was superior to MET? alone in terms of weight loss, the reduction of waist circumference, and BMI. More large-scale, high-quality RCTs are needed to further confirm these results in PCOS patients.

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Combination therapy with GLP-1 receptor agonists and basal insulin: a systematic review of the literature.

Publications

Combination therapy with GLP-1 receptor agonists and basal insulin: a systematic review of the literature.

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