Dataset Information

Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence.

ABSTRACT:

Background

In clinical trials enrolling patients with type 2 diabetes (T2D) at high cardiovascular risk, many glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved albuminuria status and possibly mitigated kidney function loss. However, limited data are available regarding the effects of GLP-1 RAs on albuminuria status and kidney function in real-world settings, including populations with a lower baseline cardiovascular and kidney risk. We assessed the association of GLP-1 RAs initiation with long-term kidney outcomes in the Maccabi Healthcare Services database, Israel.

Methods

Adults with T2D treated with ≥ 2 glucose-lowering agents who initiated GLP-1 RAs or basal insulin from 2010 to 2019 were propensity-score matched (1:1) and followed until October 2021 (intention-to-treat [ITT]). In an as-treated (AT) analysis, follow-up was also censored at study-drug discontinuation or comparator-initiation. We assessed the risk of a composite kidney outcome, including confirmed ≥ 40% eGFR loss or end-stage kidney disease, and the risk of new macroalbuminuria. Treatment-effect on eGFR slopes was assessed by fitting a linear regression model per patient, followed by a t-test to compare the slopes between the groups.

Results

Each propensity-score matched group constituted 3424 patients, 45% women, 21% had a history of cardiovascular disease, and 13.9% were treated with sodium-glucose cotransporter-2 inhibitors at baseline. Mean eGFR was 90.6 mL/min/1.73 m² (SD 19.3) and median UACR was 14.6 mg/g [IQR 0.0-54.7]. Medians follow-up were 81.1 months (ITT) and 22.3 months (AT). The hazard-ratios [95% CI] of the composite kidney outcome with GLP-1 RAs versus basal insulin were 0.96 [0.82-1.11] (p = 0.566) and 0.71 [0.54-0.95] (p = 0.020) in the ITT and AT analyses, respectively. The respective HRs for first new macroalbuminuria were 0.87 [0.75-0.997] and 0.80 [0.64-0.995]. The use of GLP-1 RA was associated with a less steep eGFR slope compared with basal insulin in the AT analysis (mean annual between-group difference of 0.42 mL/min/1.73 m²/year [95%CI 0.11-0.73]; p = 0.008).

Conclusion

Initiation of GLP-1 RAs in a real-world setting is associated with a reduced risk of albuminuria progression and possible mitigation of kidney function loss in patients with T2D and mostly preserved kidney function.

SUBMITTER: Schechter M

PROVIDER: S-EPMC10225085 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence.

Schechter Meir M Melzer Cohen Cheli C Fishkin Alisa A Rozenberg Aliza A Yanuv Ilan I Sehtman-Shachar Dvora R DR Chodick Gabriel G Clark Alice A Abrahamsen Trine J TJ Lawson Jack J Karasik Avraham A Mosenzon Ofri O

Cardiovascular diabetology 20230527 1

<h4>Background</h4>In clinical trials enrolling patients with type 2 diabetes (T2D) at high cardiovascular risk, many glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved albuminuria status and possibly mitigated kidney function loss. However, limited data are available regarding the effects of GLP-1 RAs on albuminuria status and kidney function in real-world settings, including populations with a lower baseline cardiovascular and kidney risk. We assessed the association of GLP-1 RAs i ...[more]

PMID: 37244998

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Project description:INTRODUCTION:Treatment guidelines recommend a stepwise approach to glycemia management in patients with type 2 diabetes (T2D), but this may result in uncontrolled glycated hemoglobin A1c (HbA1c) between steps. This retrospective analysis compared clinical and economic outcomes among patients with uncontrolled T2D initiating two oral antidiabetes drugs (OADs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), or basal insulin in a real-world setting. METHODS:Adults with T2D on OAD monotherapy were identified in the MarketScan claims database (2007-2014). Those initiating two OADs (simultaneously or sequentially), GLP-1 RAs, or basal insulin were selected (date of initiation was termed the 'index date'); patients were required to have HbA1c > 7.0% in the 6 months pre-index date. HbA1c was compared from 6 months pre- to 1-year post-index. Annual all-cause healthcare utilization and costs were reported over the 1-year follow-up period. RESULTS:Data for 6054 patients were analyzed (2-OAD, n = 4442; GLP-1 RA, n = 361; basal insulin, n = 1251). Baseline HbA1c was high in all cohorts, but highest in the basal-insulin cohort. Treatment initiation resulted in reductions in HbA1c in all cohorts, which was generally maintained throughout the follow-up period. Average HbA1c reductions from the 6 months pre- to 1 year post-index date were -1.2% for GLP-1 RA, -1.6% for OADs, and -1.8% for basal insulin. HbA1c < 7.0% at 1 year occurred in 32.6%, 47.5%, and 41.1% of patients, respectively. Annual healthcare costs (mean [SD]) were lowest for OAD (US$10,074 [$22,276]) followed by GLP-1 RA (US$14,052 [$23,829]) and basal insulin (US$18,813 [$37,332]). CONCLUSION:Despite robust HbA1c lowering following treatment initiation, many patients did not achieve HbA1c < 7.0%. Basal insulin, generally prescribed for patients with high baseline HbA1c, was associated with a large reduction in HbA1c and with higher costs. Therapy intensification at an appropriate time could lead to clinical and economic benefits and should be investigated further. FUNDING:Sanofi U.S., Inc.

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.

Dataset Information

Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence.

Background

Methods

Results

Conclusion

Publications

Kidney function loss and albuminuria progression with GLP-1 receptor agonists versus basal insulin in patients with type 2 diabetes: real-world evidence.

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