The type 2 diabetes drug liraglutide (Victoza) may help prevent the progression of peripheral artery disease (PAD), the small, open-label STARDUST trial suggests.

Adults with type 2 diabetes receiving subcutaneous liraglutide had a significant increase in transcutaneous oxygen pressure (TcPO2) over 6 months compared to conventional treatment (14.2 mmHg vs. 2.9 mmHg, estimated treatment difference 11.2 mmHg; 95% CI 8.0 to 14.5 mmHg). According to Dr. Maria Aida Maiorino and her colleagues at the University of Campania Luigi Vanvitelli in Naples, Italy.

A total of 89% of liraglutide patients achieved the common endpoint (10% increase in TcPO2 from baseline), compared with only 46% of controls (relative risk 1.91, 95% CI 1.26-2.90), researchers said. reported. JAMA network open.

“According to these data, administration of GLP-1 RA [receptor agonists] “This finding may point to a suitable strategy for patients with PAD and diabetes to determine the reduction or delay of the onset of lower extremity complications,” the researchers wrote. “The diagnosis of PAD can often be associated with the prevention of clinical progression of PAD”, which occurs with the appearance of severe limb ischemia or gangrene, usually leading to lower limb amputation. ”

They noted that PAD-related amputations in patients with diabetes commonly lead to permanent disability and add a significant economic burden to the healthcare system.

The researchers noted that the increase in TcPO2 was “consistent over time within the liraglutide group and was significantly different when compared to individuals randomized to the control group,” which suggests that this is associated with type 2 diabetes. It added that this was the first study in patients with PAD and showed that: Liraglutide increased peripheral blood flow.

“Liraglutide, like other GLP-1 RAs, may determine its effect on peripheral perfusion through both microvascular and macrovascular mechanisms,” the researchers wrote. “Liraglutide is effective in glucometabolic outlook, which affects cardiovascular risk profile.”

GLP-1 RA was first established for type 2 diabetes and has recently become popular for weight management. Liraglutide was first approved by the FDA for his type 2 diabetes in 2010 at his 1.8 mg dose. Liraglutide (Saxenda) was approved in 2014 for chronic weight management in adults at a dose of 3 mg, and was expanded to include teens in 2020.

More recently, this class of drugs has moved into the cardiovascular protection field, with the GLP-1 receptor agonist semaglutide (Wegovy) leading to increased risk of cardiovascular death, heart attack, and cardiovascular death in obese or overweight adults with cardiovascular disease. , approved to reduce the risk of stroke. .

In the STARDUST study, Maiorino’s group noted several other important changes in mean values ​​from baseline after 6 months of treatment.

• HbA1c: liraglutide group -0.4% vs control group -0.02
• Weight: -2.3 kg (5.1 lb) vs -1.2 kg (2.6 lb)
• BMI: -1.1 vs -0.3
• Systolic blood pressure: -5.4 mmHg vs -5.3 mmHg
• C-reactive protein: -0.4 mg/dL vs -0.03 mg/dL
• Urinary albumin to creatinine ratio: -90.5 mg/g vs. 28.8 mg/g
• 6 minute walk test: 364.0 m vs 340.1 m

Compared with the control group, liraglutide-treated patients had significantly greater decreases in C-reactive protein, interleukin-6, luteinizing hormone, urinary albumin-to-creatinine ratio, and 6-minute walking distance.

The researchers said these results “suggest a potential beneficial effect of liraglutide in improving endothelial function in patients with type 2 diabetes and PAD,” but by the end of the study, They also noted that there were no significant differences in metabolic status.

The final analysis evaluated 55 participants (27 randomized to liraglutide and 28 to the control group) enrolled in Italy from February 2021 to June 2022. Mean age at baseline was 67.5 years, and 78% were male.

Median HbA1c level was 6.9% and mean TcPO2 level was 40.3 mmHg. All patients were required to have her TcPO2 in the legs between 49 and 30 mmHg at the screening visit and her HbA1c between 6.5 and 8% while on stable hypoglycemic medication. Patients who used her GLP-1 receptor agonist within the past 3 months were excluded.

Patients in the liraglutide group started subcutaneous liraglutide 0.6 mg once daily at approximately the same time each day and increased the dose in 0.6 mg increments over a 1-week schedule to a target dose of 1.8 mg or maximum tolerated dose. Patients in the control group received conventional treatment for cardiovascular risk factors. Patients in both groups were given individualized treatment regimens to manage blood sugar levels and cardiovascular risk factors.

Although the epidemiology of PAD tends to be male-dominated, the sample size and small number of women were noted as limitations of this study.