Dataset Information

Addition of dipeptidyl peptidase-4 inhibitors to insulin treatment in type 2 diabetes patients: A meta-analysis.

ABSTRACT:

Aims/introduction

To evaluate the efficacy and safety of combining insulin therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors compared with combining insulin therapy with a placebo or other antihyperglycemic agents.

Materials and methods

A literature search was carried out via electronic databases. The inclusion criteria were randomized controlled trials comparing the addition of DPP-4 inhibitors to insulin with the addition of a placebo or other active hypoglycemic agents to insulin therapy, study duration of no less than 12 weeks carried out in type 2 diabetes patients and the availability of outcome data to evaluate a change in the glycated hemoglobin.

Results

The glycated hemoglobin-lowering efficacy was significantly greater with DPP-4 inhibitor/insulin (DPP-4i/INS) than with placebo/insulin (weighted mean difference -0.53%, 95% confidence interval -0.63, -0.43, P < 0.01). The postprandial plasma glucose-lowering efficacies was also significantly greater with DPP-4i/INS than with placebo/insulin (weighted mean difference -1.65 mmol/L, 95% CI: -2.34, -0.96, P < 0.05). The risk of hypoglycemia or severe hypoglycemia was similar for DPP4i/INS and placebo/insulin treatments. There was no significant difference in the glycemia-lowering efficacy between DPP-4i/INS and alpha-glucosidase inhibitors/insulin, thiazolidinedione/insulin and glucagon-like peptide-1 receptor agonist/insulin. Sodium-glucose cotransporter 2 inhibitor/insulin treatment achieved better placebo-corrected efficacy in lowering postprandial plasma glucose, with less weight gain and no higher risk of hypoglycemia.

Conclusions

Treatment with DPP-4 inhibitors combined with insulin improved glycemic control without an increased risk of hypoglycemia or weight gain compared with insulin treatment alone.

SUBMITTER: Yang W

PROVIDER: S-EPMC6031492 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Addition of dipeptidyl peptidase-4 inhibitors to insulin treatment in type 2 diabetes patients: A meta-analysis.

Yang Wenjia W Cai Xiaoling X Gao Xueying X Chen Yifei Y Chen Ling L Ji Linong L

Journal of diabetes investigation 20171205 4

<h4>Aims/introduction</h4>To evaluate the efficacy and safety of combining insulin therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors compared with combining insulin therapy with a placebo or other antihyperglycemic agents.<h4>Materials and methods</h4>A literature search was carried out via electronic databases. The inclusion criteria were randomized controlled trials comparing the addition of DPP-4 inhibitors to insulin with the addition of a placebo or other active hypoglycemic agents to ...[more]

PMID: 29047219

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Project description:Type 2 diabetes mellitus is a complex and progressive disease that is showing an apparently unstoppable increase worldwide. Although there is general agreement on the first-line use of metformin in most patients with type 2 diabetes, the ideal drug sequence after metformin failure is an area of increasing uncertainty. New treatment strategies target pancreatic islet dysfunction, in particular gut-derived incretin hormones. Inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4) slows degradation of endogenous glucagon-like peptide-1 (GLP-1) and thereby enhances and prolongs the action of the endogenous incretin hormones. The five available DPP-4 inhibitors, also known as 'gliptins' (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin), are small molecules used orally with similar overall clinical efficacy and safety profiles in patients with type 2 diabetes. The main differences between the five gliptins on the market include: potency, target selectivity, oral bioavailability, long or short half-life, high or low binding to plasma proteins, metabolism, presence of active or inactive metabolites, excretion routes, dosage adjustment for renal and liver insufficiency, and potential drug-drug interactions. On average, treatment with gliptins is expected to produce a mean glycated hemoglobin (HbA1c) decrease of 0.5%-0.8%, with about 40% of diabetic subjects at target for the HbA1c goal <7%. There are very few studies comparing DPP-4 inhibitors. Alogliptin as monotherapy or added to metformin, pioglitazone, glibenclamide, voglibose, or insulin therapy significantly improves glycemic control compared with placebo in adult or elderly patients with inadequately controlled type 2 diabetes. In the EXAMINE trial, alogliptin is being compared with placebo on cardiovascular outcomes in approximately 5,400 patients with type 2 diabetes. In clinical studies, DPP-4 inhibitors were generally safe and well tolerated. However, there are limited data on their tolerability, due to their relatively recent marketing approval. Alogliptin will be used most when avoidance of hypoglycemic events is paramount, such as in patients with congestive heart failure, renal failure, and liver disease, and in the elderly.

Project description:ObjectiveTo quantify the risk of hypoglycaemia associated with the concomitant use of dipeptidyl peptidase-4 (DPP-4) inhibitors and sulphonylureas compared with placebo and sulphonylureas.DesignSystematic review and meta-analysis.Data sourcesMedline, ISI Web of Science, SCOPUS, Cochrane Central Register of Controlled Trials, and clinicaltrial.gov were searched without any language restriction.Study selectionPlacebo controlled randomised trials comprising at least 50 participants with type 2 diabetes treated with DPP-4 inhibitors and sulphonylureas.Review methodsRisk of bias in each trial was assessed using the Cochrane Collaboration tool. The risk ratio of hypoglycaemia with 95% confidence intervals was computed for each study and then pooled using fixed effect models (Mantel Haenszel method) or random effect models, when appropriate. Subgroup analyses were also performed (eg, dose of DPP-4 inhibitors). The number needed to harm (NNH) was estimated according to treatment duration.Results10 studies were included, representing a total of 6546 participants (4020 received DPP-4 inhibitors plus sulphonylureas, 2526 placebo plus sulphonylureas). The risk ratio of hypoglycaemia was 1.52 (95% confidence interval 1.29 to 1.80). The NNH was 17 (95% confidence interval 11 to 30) for a treatment duration of six months or less, 15 (9 to 26) for 6.1 to 12 months, and 8 (5 to 15) for more than one year. In subgroup analysis, no difference was found between full and low doses of DPP-4 inhibitors: the risk ratio related to full dose DPP-4 inhibitors was 1.66 (1.34 to 2.06), whereas the increased risk ratio related to low dose DPP-4 inhibitors did not reach statistical significance (1.33, 0.92 to 1.94).ConclusionsAddition of DPP-4 inhibitors to sulphonylurea to treat people with type 2 diabetes is associated with a 50% increased risk of hypoglycaemia and to one excess case of hypoglycaemia for every 17 patients in the first six months of treatment. This highlights the need to respect recommendations for a decrease in sulphonylureas dose when initiating DPP-4 inhibitors and to assess the effectiveness of this risk minimisation strategy.

Dataset Information

Addition of dipeptidyl peptidase-4 inhibitors to insulin treatment in type 2 diabetes patients: A meta-analysis.

Aims/introduction

Materials and methods

Results

Conclusions

Publications

Addition of dipeptidyl peptidase-4 inhibitors to insulin treatment in type 2 diabetes patients: A meta-analysis.

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