SGLT2 inhibitor use associated with lower risk of cancer

9th June 2023

SGLT2 inhibitor drug use in patients with diabetes appears to reduce cancer risk, according to a retrospective analysis by Taiwanese researchers.

Epidemiological evidence suggests that diabetes increases the risk of cancer. It is thought the combination of hyper-insulinaemia, chronic inflammation and hyperglycaemia could increase the growth of tumours. Consequently, it may be possible to reduce this risk with anti-diabetic treatment. A recent meta-analysis of randomised clinical trials, suggests that SGLT2 inhibitor drugs could lower cancer risk compared to placebo. However, the extent to which these drugs might reduce the risk of cancer in practice is less clear.

The current study, published in the Journal of Diabetes and its Complications, retrospectively compared cancer development among SGLT2 inhibitor users. The team matched these patients with a group not prescribed these drugs. The primary outcome was cancer development and the analysis adjusted for several potential confounders.

SGLT2 inhibitor use and cancer risk

A cohort of 325,990 SGLT2 inhibitor users with mean age of 58.6 years (42.2% female) and 325,989 non-users was identified.

SGLT2 inhibitor users had a significantly lower cancer risk (adjusted hazard ratio, aHR = 0.79, 95% CI 0.76 – 0.83) than non-users. The risk of cancer was also higher among males (aHR = 1.35, 95% CI 1.30 – 1.41) and in patients aged 50-64 and older than 65 years.

Researchers also noticed that this risk reduction was dependent on the duration of SGLT2 inhibitor use. Short-term use (60-140 days) was actually linked to a higher cancer risk (aHR = 1.30, 95% CI 1.21 – 1.39).

In addition, while cancer risk was generally lower, there was a significant increased risk of pancreatic cancer (aHR = 1.51, 95% CI 1.22 – 1.87) which was consistent with the findings of a recent case study.

SGLT-2 inhibition lowers stroke risk in people with diabetes plus atrial fibrillation

1st June 2023

SGLT-2 inhibitor use in people with both diabetes and atrial fibrillation reduces the risk of ischaemic strokes, according to the results of a longitudinal follow‐up study.

Atrial fibrillation (AF) is the most common global cardiac arrhythmia, affecting over three million people. Having AF increases the risk of ischaemic stroke with this risk stratified by the CHA₂DS₂-VASc score. Fasting hyperglycaemia is a risk factor for AF although the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduces this risk.

The researchers considered whether SGLT-2 inhibitors could therefore reduce the risk of ischaemic stroke in diabetics with AF. Published in the Journal of the American Heart Association, the Taiwanese study followed a group of patients with both diabetes and AF who were prescribed either empagliflozin or dapagliflozin. These individuals were propensity matched to non-users and the incidence of ischaemic strokes documented over the next five years.

SGLT-2 inhibitor use and ischaemic stroke

A total of 6,614 patients, 801 prescribed one of the SGLT-2 inhibitors, had usable data for analysis.

After five years, 809 patients with diabetes and AF developed an ischaemic stroke. However, the rate was significantly lower among SGLT-2 inhibitor users (p = 0.021).

As expected, there was an increased risk of stroke per one-point increase CHA₂DS₂‐VASc score (hazard ratio, HR = 1.24, 95% CI 1.20 – 1.29, p < 0.001). Adjusting for the CHA₂DS₂‐VASc score lowered the stroke risk by 20% among SGLT-2 inhibitor users (HR= 0.80, 95% CI 0.64 – 0.99, p = 0.043).

The findings prompted the authors to suggest clinicians upgrade SGLT-2 inhibitors for glycaemic control, especially in those with co-existing AF.

SGLT-2 inhibitors and metformin have similar cardiovascular outcomes in type 2 diabetes

31st May 2022

SGLT-2 inhibitors and metformin have similar CV outcomes in type 2 diabetes though SGLT-2 inhibitors slightly lower heart failure mortality

SGLT-2 inhibitors and metformin when initiated for patients with type 2 diabetes have been shown to have the same cardiovascular outcomes such as myocardial infarction, stroke and death although use of SFLT-2 inhibitors is associated with a slightly lower risk of both hospitalisation and death due to heart failure.

These were the key findings from a cohort study analysis by a team based at Harvard University, Boston, USA.

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) such as empagliflozin, although primarily used in the management of type 2 diabetes, have also been shown to reduce cardiovascular events when added to standard care.

In addition, evidence from the UK Prospective Diabetes Study showed that patients assigned to metformin had risk reductions of 32% for any diabetes-related endpoint, 42% for diabetes-related death and 36% for all-cause mortality.

Thus, although SGLT-2 inhibitors and metformin are primarily diabetic treatments, it is apparent that both are associated with cardiovascular benefits in diabetic patients. Furthermore, using SGLT-2 inhibitors and metformin as a first-line combination therapy for patients with type 2 diabetes has been suggested as a cost-effective strategy for the management of both type2 diabetes and cardiovascular disease.

However, what remains uncertain, is the relative cardiovascular benefits of using either a SGLT-2 inhibitor or metformin as mono-therapy in patients with type 2 diabetes.

In the present study, the US team used information held within two large commercial health insurance databases to compare the incidence of cardiovascular events when either treatment was initiated as mono-therapy.

The researchers focused on adults (> 18 years of age) with a diagnosis of type 2 diabetes and those who had new prescription for SGLT-2 inhibitors or metformin. Individuals were followed-up until the occurrence of a study outcome, death or discontinuation of treatment.

There were two primary outcomes of interest; a composite of acute myocardial infarction, stroke or all-cause mortality (referred to as ‘mortality’) and a composite of hospitalisation for heart failure or all-cause mortality (HHF).

For secondary outcomes, the authors individually assessed the effect of either treatment on different components of the two composites. Individuals were propensity-matched 1:2 (SGLT-2i: metformin).

SGLT-2 inhibitors and metformin

A total of 8,613 first-time SGLT-2i patients were matched to 17,226 metformin users, with a mean age of 60 years (approximately 51% male). Individuals prescribed SGLT-2i were followed for a mean of 10.7 months and metformin users for 12.2 months.

The risk of the composite mortality outcome was not significantly different between the two treatments (hazard ratio, HR = 0.96, 95% CI 0.77 – 1.19). However, SGLT-2i inhibitor use was associated with a lower risk of HHF (HR = 0.80, 95% CI 0.66 – 0.97).

When each of the outcomes were analysed separately, only hospitalisation for heart failure was significantly lower (HR = 0.78, 95% CI 0.62 – 0.97) in those prescribed a SGLT-2i.

Based on these findings, the authors concluded that first-line treatment of type 2 diabetes with SGLT-2i or metformin was associated with a similar risk of adverse cardiovascular outcomes although SGLT-2i use was linked to a lower risk of hospitalisation and mortality due to heart failure. However, they called for a randomised trial to provide more robust evidence to confirm these findings.

Citation
Shin JH et al. Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors Versus Metformin. A Cohort Study Ann Intern Med 2022