A multinational study involving Australian researchers has found more evidence for cardiovascular benefits associated with the newest group of oral medications used to treat type 2 diabetes
New research has provided further support for cardiovascular benefits associated with sodium-glucose co-transporter-2 (SGLT2) inhibitors, which are glucose-lowering drugs widely used in the treatment of type 2 diabetes.
People with type 2 diabetes are at increased risk of cardiovascular events, with cardiovascular mortality the leading cause of death in this group of patients.
In a new study, researchers from 13 countries have directly compared the risk of cardiovascular events and death in type 2 diabetes patients using SGLT2 inhibitors versus those using DPP-4 inhibitors, another group of oral medications used to treat type 2 diabetes.
To date, DPP-4 inhibitors have shown no effect on ischaemic events or cardiovascular death, and, for the most widely used DPP-4 inhibitor—sitagliptin—no effect on hospitalisation for heart failure, according to the researchers.
Meanwhile previous studies involving clinical trials have shown SGLT2 inhibitors significantly reduce the risk of heart failure, kidney disease, myocardial infarction, stroke and death, say the researchers (see here, here, here and here).
The multinational comparative cohort study used data from nearly 400,000 patients who were initiated on the two drug classes between Dec 2012, and May 2016, with follow-up until Dec 2014 to Nov 2017 (full range; dates varied by country).
Patients who were initiated on an SGLT2 inhibitor were matched with those who were initiated on a DPP-4 inhibitor in a 1:1 ratio, according to the study published in The Lancet, Diabetes & Endocrinology.
“The global team used data from a wide range of geographical locations comprising the Asia-Pacific, the Middle East, Europe, and North America – this included 193,124 new users of SGLT2 inhibitors and 193,124 new users of DPP-4 inhibitors, so it was a pretty significant undertaking,” explains co-author Dr Jenni Ilomaki from Monash University’s Centre for Medicine Use and Safety, one of the Australian centres working on the research alongside the Baker Institute.
Data for the Australian component to the study was obtained from the National Diabetes Services Scheme, National Death Index and the Pharmaceutical Benefits Scheme.
Participants had a mean age of 58 years, 44·1% were women and 30·1 % had established cardiovascular disease.
Results showed initiation of an SGLT2 inhibitor versus a DPP-4 inhibitor was associated with substantially lower risks of hospitalisation for heart failure (HR 0·69, 95% CI 0·61–0·77; p<0·0001), all-cause death (0·59, 0·52–0·67; p<0·0001), and the composite of hospitalisation for heart failure or all-cause death (0·64, 0·57–0·72; p<0·0001).
Risks of myocardial infarction (HR 0·88, 0·80–0·98; p=0·020) and stroke (0·85 0·77–0·93; p=0·0004) were significantly, but modestly, lower with SGLT2 inhibitors versus DPP-4 inhibitors.
“Our research is important because it was unclear whether the benefits demonstrated in previous randomised controlled trials of SGLT2 inhibitors are achieved in routine clinical practice,” Dr Ilomaki told AJP.
This study involved an active comparison group, whereas previous randomised controlled trials have been placebo controlled, she noted.
“It was a multidatabase study conducted in 13 different countries. The results were quite consistent across countries despite differences in the regulatory systems and prescribing practices, particularly for the outcomes of heart failure and all-cause mortality. This suggests that the findings are widely generalisable across different settings,” said Dr Ilomaki.
The Baker Institute’s Deputy Director, Clinical and Population Health, Professor Jonathan Shaw, says it’s promising to see benefits being shown outside of a controlled clinical trial environment.
“This study shows the benefits that were seen in clinical trials are also occurring in the real world. Furthermore, while clinical trials mainly focused on those at very high cardiovascular risk, this study also observed benefits for people with more moderate levels of risk,” Professor Shaw said.
In Australia, SGLT2 inhibitors are considered as ‘second line’ treatment, which means they are commenced as an add-on treatment after standard treatment with metformin or sulfonylurea has been first trialled – medicines widely prescribed to manage type 2 diabetes.
“Diabetes and heart diseases are national health priorities in Australia and our study highlights the importance of pharmacists promoting adherence to these newer evidence-based treatments at the point of dispensing,” said Dr Ilomaki.
“The study findings also have direct implications for pharmacists who are increasingly working with patients and other health professionals to optimise the management of diabetes and heart disease through medication management reviews and other services,” she said.
The next step in their research is to investigate newer diabetes medications and clinical outcomes in vulnerable patient populations.
This will be done through a newly established 10-country ‘big data’ platform called NeuroGEN for investigating medication safety and effectiveness in Australia, Asia, Europe and the Americas.
See the full article here (online 16 June 2020; login required). Note: the research was funded by AstraZeneca.