Dataset Information

Cardiovascular outcomes after initiating GLP-1 receptor agonist or basal insulin for the routine treatment of type 2 diabetes: a region-wide retrospective study

ABSTRACT:

Aim

We aimed to compare cardiovascular outcomes of patients with type 2 diabetes (T2D) who initiated GLP-1 receptor agonists (GLP-1RA) or basal insulin (BI) under routine care.

Methods

We accessed the administrative claims database of the Veneto Region (Italy) to identify new users of GLP-1RA or BI in 2014–2018. Propensity score matching (PSM) was implemented to obtain two cohorts of patients with superimposable characteristics. The primary endpoint was the 3-point major adverse cardiovascular events (3P-MACE). Secondary endpoints included 3P-MACE components, hospitalization for heart failure, revascularizations, and adverse events.

Results

From a background population of 5,242,201 citizens, 330,193 were identified as having diabetes. PSM produced two very well matched cohorts of 4063 patients each, who initiated GLP-1RA or BI after an average of 2.5 other diabetes drug classes. Patients were 63-year-old and only 15% had a baseline history of cardiovascular disease. During a median follow-up of 24 months in the intention-to-treat analysis, 3P-MACE occurred less frequently in the GLP-1RA cohort (HR versus BI 0.59; 95% CI 0.50–0.71; p < 0.001). All secondary cardiovascular endpoints were also significantly in favor of GLP-1RA. Results were confirmed in the as-treated approach and in several stratified analyses. According to the E-value, confounding by unmeasured variables were unlikely to entirely explain between-group differences in cardiovascular outcomes.

Conclusions

Patients with T2D who initiated a GLP-1RA experienced far better cardiovascular outcomes than did matched patients who initiated a BI in the same healthcare system. These finding supports prioritization of GLP-1RA as the first injectable regimen for the management of T2D.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12933-021-01414-3.

SUBMITTER: Longato E

PROVIDER: S-EPMC8590792 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description: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.

Project description:ContextNovel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide demonstrated substantially greater glucose control and weight loss (WL) compared with selective GLP-1RA dulaglutide.ObjectiveExplore mechanisms of glucose control by tirzepatide.DesignPost hoc analyses of fasting biomarkers and multiple linear regression analysis.SettingForty-seven sites in 4 countries.Patients or other participantsThree hundred and sixteen subjects with type 2 diabetes.InterventionsTirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), placebo.Main outcome measuresAnalyze biomarkers of beta-cell function and insulin resistance (IR) and evaluate WL contributions to IR improvements at 26 weeks.ResultsHomeostatic model assessment (HOMA) 2-B significantly increased with dulaglutide and tirzepatide 5, 10, and 15 mg compared with placebo (P ≤ .02). Proinsulin/insulin and proinsulin/C-peptide ratios significantly decreased with tirzepatide 10 and 15 mg compared with placebo and dulaglutide (P ≤ .007). Tirzepatide 10 and 15 mg significantly decreased fasting insulin (P ≤ .033) and tirzepatide 10 mg significantly decreased HOMA2-IR (P = .004) compared with placebo and dulaglutide. Markers of improved insulin sensitivity (IS) adiponectin, IGFBP-1, and IGFBP-2 significantly increased by 1 or more doses of tirzepatide (P < .05). To determine whether improvements in IR were directly attributable to WL, multiple linear regression analysis with potential confounding variables age, sex, metformin, triglycerides, and glycated hemoglobin A1c was conducted. WL significantly (P ≤ .028) explained only 13% and 21% of improvement in HOMA2-IR with tirzepatide 10 and 15 mg, respectively.ConclusionsTirzepatide improved markers of IS and beta-cell function to a greater extent than dulaglutide. IS effects of tirzepatide were only partly attributable to WL, suggesting dual receptor agonism confers distinct mechanisms of glycemic control.