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

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.

SGLT2is vs. GLP1RAs Reduce Cardiovascular and All-Cause Mortality

“…In this meta-analysis we included 9 large PSM cohort studies (4)(5)(6)(7)(8)(9)(10)(11)(12). Each of included studies was assessed as high quality according to NOS.…”

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

“…In the absence of evidence from RCTs, real-world studies on hard outcomes have compared several classes of glucose-lowering medications, including GLP-1RA, dipeptidyl-peptidase 4 inhibitors (DPP-4i), and sodium glucose cotransporter-2 inhibitors (SGLT2i). Patients initiating GLP-1RA under free-living conditions had better cardiovascular outcomes compared to those initiating DPP-4i [ 11 ], whereas the comparison between GLP-1RA and SGLT2i yielded mixed results according to the setting and duration of observation [ 12 – 15 ].…”

Comparative effectiveness of SGLT2i versus GLP1-RA on cardiovascular outcomes in routine clinical practice

“…A few observational studies have compared the effects of SGLT2i and GLP1-RA [36][37][38][39], with somewhat varying findings. An analysis of the Swedish Diabetes registry found a similar risk of MACE, cardiovascular death and myocardial infarction, but an increased risk of stroke for SGLT2i versus GLP1-RA [37], which aligns with our analysis.…”