Cardiorenal and other diabetes related outcomes with SGLT-2 inhibitors compared to GLP-1 receptor agonists in type 2 diabetes: nationwide observational study - PubMed (original) (raw)

Observational Study

Moa Lugner et al. Cardiovasc Diabetol. 2021.

Abstract

Background: Major prospective randomized clinical safety trials have demonstrated beneficial effects of treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) in people with type 2 diabetes and elevated cardiovascular risk, and recent clinical treatment guidelines therefore promote early use of these classes of pharmacological agents. In this Swedish nationwide observational study, we compared cardiorenal outcomes and safety of new treatment with GLP-1RA and SGLT-2i in people with type 2 diabetes.

Methods: We linked data from national Swedish databases to capture patient characteristics and outcomes and used propensity-score based matching to account for differences between the two groups. The treatments were compared using Cox regression models.

Results: We identified 9648 participants starting GLP-1RA and 12,097 starting SGLT-2i with median follow-up times 1.7 and 1.1 years, respectively. The proportion of patients with a history of MACE were 15.8%, and 17.0% in patients treated with GLP-1RA and SGLT-2i, respectively. The mean age was 61 years with 7.6 years duration of diabetes. Mean HbA1c were 8.3% (67.6 mmol/mol) and 8.3% (67.2 mmol/mol), and mean BMI 33.3 and 32.5 kg/m2 in patients treated with GLP-1RA or SGLT-2i, respectively. The cumulative mortality risk was non-significantly lower in the group treated with SGLT-2i, HR 0.78 (95% CI 0.61-1.01), as were incident heart failure outcomes, but the risks of cardiovascular or renal outcomes did not differ. The risks of stroke and peripheral artery disease were higher in the SGLT-2i group relative to GLP-1RA, with HR 1.44 (95% CI 0.99-2.08) and 1.68 (95% CI 1.04-2.72), respectively.

Conclusions: This observational study suggests that treatment with GLP-1RA and SGLT-2i result in very similar cardiorenal outcomes. In the short term, treatment with GLP-1RA seem to be associated with lower risks of stroke and peripheral artery disease, whereas SGLT-2i seem to be nominally associated with lower risk of heart failure and total mortality.

Keywords: Cardiovascular disease; Epidemiology; Glucagon‐like peptide-1 receptor agonist; Mortality; Sodium glucose transporter 2 inhibitors; Type 2 diabetes.

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Conflict of interest statement

Professor Eliasson reports personal fees (expert panels, lectures) from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Mundipharma, Navamedic, NovoNordisk, RLS Global, grants and personal fees from Sanofi, all outside the submitted work. Naveed Sattar has received honoraria from Merck, GSK, MSD, and Novo Nordisk. Moa Lugner, Mervete Miftaraj, Jan Ekelund, Stefan Franzén and Ann-Marie Svensson declare that they have no competing interests.

Figures

Fig. 1

Fig. 1

Outcome analysis. Results of Cox analysis on primary and secondary outcomes. Event rates are reported as number of events/1000 person-years

Fig. 2

Fig. 2

a Cumulative total mortality (IPTW) after starting treatment with a GLP-1RA or a SGLT-2i. b Cumulative incidence rates of MACE (IPTW) after starting treatment with a GLP-1RA or a SGLT-2i. HRs SGLT-2 inhibitor vs. GLP-1 receptor agonist 1.03 (0.89–1.21). c Cumulative incidence stroke (IPTW) after starting treatment with a GLP-1RA or a SGLT-2i. HRs SGLT-2 inhibitor vs. GLP-1 receptor agonist 1.44 (0.99–2.08). d Cumulative incidence rates of retinopathy (IPTW) after starting treatment with a GLP-1RA or a SGLT-2i. HRs SGLT-2 inhibitor vs. GLP-1 receptor agonist 2.15 (0.92–5.03). e Cumulative incidence rates of peripheral artery disease (IPTW) after starting treatment with a GLP-1RA or a SGLT-2i. HRs SGLT-2 inhibitor vs. GLP-1 receptor agonist 1.68 (1.04–2.72). f Cumulative incidence rates of congestive heart failure (IPTW) after starting treatment with a GLP-1RA or a SGLT-2i. HRs SGLT-2 inhibitor vs. GLP-1 receptor agonist 0.83 (0.65–1.07)

Fig. 2

Fig. 2

a Cumulative total mortality (IPTW) after starting treatment with a GLP-1RA or a SGLT-2i. b Cumulative incidence rates of MACE (IPTW) after starting treatment with a GLP-1RA or a SGLT-2i. HRs SGLT-2 inhibitor vs. GLP-1 receptor agonist 1.03 (0.89–1.21). c Cumulative incidence stroke (IPTW) after starting treatment with a GLP-1RA or a SGLT-2i. HRs SGLT-2 inhibitor vs. GLP-1 receptor agonist 1.44 (0.99–2.08). d Cumulative incidence rates of retinopathy (IPTW) after starting treatment with a GLP-1RA or a SGLT-2i. HRs SGLT-2 inhibitor vs. GLP-1 receptor agonist 2.15 (0.92–5.03). e Cumulative incidence rates of peripheral artery disease (IPTW) after starting treatment with a GLP-1RA or a SGLT-2i. HRs SGLT-2 inhibitor vs. GLP-1 receptor agonist 1.68 (1.04–2.72). f Cumulative incidence rates of congestive heart failure (IPTW) after starting treatment with a GLP-1RA or a SGLT-2i. HRs SGLT-2 inhibitor vs. GLP-1 receptor agonist 0.83 (0.65–1.07)

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