Prevalence of eligibility for dual GIP/GLP-1 receptor agonists among non-diabetic and overweight adults - a Portuguese community-based study

Background

Obesity stands as a potentially modifiable cardiovascular (CV) risk factor, with current guidelines including targeted therapy as part of standard of care. Recent evidence shows benefits of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists (RA) therapy in overweight and non-diabetic individuals, with significant weight loss and improved CV markers. In Portugal, reimbursement of GLP-1 RA therapy is restricted to individuals with concomitant grade II obesity and type 2 diabetes, leaving many undertreated.

Purpose

To assess and characterize the prevalence of non-diabetic and overweight adults potentially eligible for dual GIP/GLP-1 RA therapy in a community-based setting.

Methods

A cross-sectional CV screening programme was conducted in three localities in Portugal. Screening included a standardized clinical assessment and onsite blood sampling. Eligibility for dual RA therapy with tirzepatide followed SURMOUNT-1 Trial (NCT04184622) criteria.

Results

A total of 161 non-diabetic pts were included (out of 198 screened pts), mostly female (n=110, 68%), median age of 65 years (IQR 56,73) and median body mass index (BMI) of 27 Kg/m2 (IQR 24,29). Nearly half (n=68, 49%) were classified as high risk according to the 10-year risk estimate of CV disease in Europe.

Based on the eligibility criteria (figure 1), more than one-third (n=62, 39%) were deemed eligible for tirzepatide, mainly due to BMI ≥ 30 Kg/m2 (n=32, 52%), followed by BMI ≥ 27 Kg/m2 with arterial hypertension and/or dyslipidemia (n=28, 46%).

Eligible pts had higher waist circumference (103 cm vs 89 cm, p<0.001), as well as higher glycated hemoglobin (5.70% vs 5.50%, p=0.004) and triglycerides levels (146 mg/dL vs 120 mg/dL, p=0.003). Possibly due to more frequent statin treatment (n=44, 71% vs n=35, 35% p<0.001), eligible pts had lower low-density lipoprotein cholesterol (81 mg/dL vs 101 mg/dL, p=0.026).

Other blood parameters, including lipoprotein(a) (21 mg/dL, p=0.7), serum creatinine (0.77 mg/dL, p=0.2), high-sensitivity c-reactive protein (1.10 mg/dL p=0.095) and N-terminal pro–B-type natriuretic peptide (79 pg/mL, p>0.9) levels were similar across groups.

Stable mental health disorders were more prevalent in eligible pts (n=21, 34% vs n=17, 17%, p=0.015) with no major differences in other chronic conditions. Although Atlantic dietary pattern (p=0.060), alcohol intake (p=0.072) and smoking history (p=0.4) were similar, eligible pts reported significantly less rates of aerobic physical activity per week (n=48, 77% vs n=92, 92%, p=0.004).

Despite the high eligibility rate, none of the pts was under dual RA therapy.

Conclusions

A substantial proportion of our community-based sample met the eligibility criteria for tirzepatide, yet none of the pts were currently under it. These findings support the need for updated health policies to possibly ensure wider access for GIP/GLP-1 therapy beyond the diabetic population.For image description, please refer to the figure legend and surrounding text.