ObjectiveTo evaluate the effect of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), compared with dipeptidyl peptidase-4 inhibitors (DPP-4i) as add-on therapy on cardiovascular (CV) morbidity and mortality in patients with type 2 diabetes (T2D).Design and settingA nationwide cohort study using three linked healthcare databases from Slovenia (outpatient prescription claims data, hospitalisation claims data and death registry data).ParticipantsPatients with T2D with newly introduced DPP-4i (n=3817), GLP-1RA (n=855) or SGLT2i (n=2851) add-on therapy between June 2014 and June 2018.Primary and secondary outcome measuresThe primary outcome was a major adverse CV event (MACE), while the secondary outcomes were CV death and heart failure (HF). The effects of the antidiabetic medicine group on the risk of each outcome were estimated with Cox proportional hazards regression. Intention-to-treat and on-treatment approaches were used.ResultsIn the intention-to-treat analysis, SGLT2i as add-on therapy, when compared with DPP-4i, was associated with lower risk of MACE (HR=0.66; 95% CI 0.50 to 0.85; p=0.002) and CV death (HR=0.46; 95% CI 0.30 to 0.73; p=0.001). On-treatment analysis revealed lower HF risk in patients initiating SGLT2i (HR=0.54; 95% CI 0.30 to 0.99; p=0.047). In the intention-to-treat analysis, GLP-1RA add-on therapy was associated with a lower MACE risk when compared with DPP-4i (HR=0.64; 95% CI 0.43 to 0.97; p=0.034), but it had a non-significant effect on CV death (HR=0.62; 95% CI 0.34 to 1.14; p=0.128) and HF (HR=1.39; 95% CI 0.88 to 2.21; p=0.157). The results of on-treatment analyses were in agreement with the results of intention-to-treat analyses.ConclusionsSGLT2i and GLP-1RA improved CV morbidity and mortality in patients with T2D when compared with DPP-4i as an add-on therapy. The results of this study may serve as a basis for the selection of an optimal add-on antidiabetic medicine to reduce CV morbidity and mortality in patients with T2D in clinical practice.Trial registration numberEUPAS32558.

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Aims To compare the influence of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of lower extremity amputations in patients with type 2 diabetes in Slovenia. Methods This retrospective cohort study included patients aged 40 years or more who were administered a newly introduced SGLT2i or DPP-4i between June 2014 and June 2018. Patients treated with insulin at baseline and patients with a history of amputation were excluded. Patients were matched in a 1:1 ratio using propensity score matching. Survival analysis was performed; hazard ratio (HR) and ratios of cumulative hazards at 1, 2, 3, and 4 years were estimated. On-treatment and intention-to-treat approaches were used. Results The study cohort (mean age: 64 years) consisted of 2,939 new users of SGLT2i (empagliflozin, 59%; dapagliflozin, 41%) matched to 2,939 new users of DPP-4i. In the on-treatment analysis (median follow-up of 2 years), the incidence of amputations was higher in SGLT2i than in DPP-4i users (4.2 vs. 2.7 per 1,000 patient years), resulting in a HR of 1.58 (95% CI 0.85–2.92; p = 0.145). An intention-to-treat analysis yielded to similar HR of 1.86 (95% CI: 1.10–3.14; p = 0.020). There was no difference in amputation rates in the first two years, but SGLT2i users had a 2.81-fold higher (95% CI: 1.63–4.84; p = 0.007) cumulative hazard of amputation at 4 years than did DPP-4i users. Conclusions Compared with DPP-4i use, SGLT2i use did not result in a statistically significant higher overall risk of lower extremity amputations. However, the results suggest that SGLT2i may increase the risk of amputation with long-term use.

The aim of the study was to assess the initiation of insulin therapy in patients with type 2 diabetes using health claims data on prescription medicines. The study evaluated time to insulin initiation and prescribing patterns of other anti-diabetic medicines before and after insulin initiation. Five years after starting non-insulin antidiabetic therapy, 6.4 % of patients were prescribed insulin, which is substantially lower compared to other similar studies. Among all patients who initiated insulin therapy in 2013, 30 % did not continue any other antidiabetic therapy. However, this proportion was lowered to 20 % in 2018. Before insulin initiation in 2018, metformin was prescribed in only 67 % of patients and sulfonylureas in 78 % of patients. Moreover, metformin and sulfonylureas were discontinued after insulin initiation in 26 and 37 % of patients, resp. More attention should be paid to the continuation of oral anti-diabetics, particularly metformin, after insulin initiation.

female) with median follow-up of 2.61 years. SH was associated with twofold risk of all-cause mortality (10.54% vs. 5.17%; HR=2.14, 95% CI 1.77-2.58, P,0.001). Patients in the SH cohort had higher incidence of transient ischemic attack compared with non-SH (10.54% vs. 8.03%; P,0.05), while the significance disappeared in the adjusted Cox analyses. No significant difference was observed for other complications. Conclusions: In Chinese patients with T2DM, severe hypoglycemia is a potent marker of increased risk of all-cause mortality, but no significant association between severe hypoglycemia with acute cardiovascular and cerebral vascular events was observed. Further studies with longer follow-up period is needed in future.