Nutritional deficiencies and muscle loss in adults with type 2 diabetes using GLP-1 receptor agonists: a retrospective observational study

Scott Butsch W, Sulo S, Chang AT, Kim JA, Kerr KW, Williams DR, et al. Obes Pillars. 2025 Jun;15:100186.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated glycaemic and weight-reduction benefits for people with type 2 diabetes mellitus (T2DM), obesity or both. The weight loss is primarily driven by fat loss; however, GLP-1 RA use can also lead to nutritional deficiencies and loss of muscle mass, particularly when not accompanied by appropriate lifestyle interventions.

Study Design

This was an observational, retrospective analysis of de-identified patient-level healthcare claims data from 461,382 US adults newly prescribed GLP-1RAs between July 2017 and December 2021 with no prior diagnoses of nutritional deficiencies. While most patients had T2DM, the population also included individuals with T1DM, prediabetes or no recorded diabetes diagnosis.

A secondary matched-cohort analysis compared GLP-1RA users with non-users. This cohort consisted of adults with T2DM treated with metformin but not prescribed GLP-1RAs (non-users). GLP-1RA users were treated with both metformin and GLP-1RA.

Nutritional deficiencies were assessed at 6 and 12 months after GLP-1RA initiation. Nutritional deficiency diagnoses or complications were compared between patients with or without a dietitian visit within 6 months of treatment initiation.

Key Findings

Patients were mostly female (56.3%), mean age 52.9 years old, had T2DM (80.5%), hypertension (66.3%) and obesity (44.9%). Most patients in the cohort (91.7%) had not visited a dietitian 6 months prior to GLP-1RA prescription.

Nutritional deficiencies were diagnosed in 12.7% of the GLP-1 RA users within 6 months after GLP-1RA initiation. This number grew to 22.4% within 12 months. Vitamin D deficiency was most common, having an incidence of 7.5% and 13.6% within 6 and 12 months, respectively. The most common deficiency-related complication was nutritional anaemia (2.1% after 6 months, 4% after 12 months), driven by iron deficiency anaemia. Additionally, 3% of patients were diagnosed with muscle loss within a year of starting GLP-1RA therapy.

Overall, a higher incidence of nutritional deficiencies was reported in GLP-1 RA users compared to non-users at 12 months (18.6% versus 16.5%, respectively; p<0.01). Key nutrient deficiencies included thiamine, other B group vitamins and vitamin D.

Identification of nutritional deficiencies in general was 1.4 to 1.5 times more likely among patients with a dietitian visit within the first 6 or 12 months of GLP-1RA initiation compared to patients without a dietitian visit (p<0.01).

Conclusion

The number of GLP-1 RA users in this study presenting with nutritional deficiencies nearly doubled during the second six months of use, highlighting the importance of nutritional screening and monitoring, as well as the potential value of nutritional therapy (e.g. multivitamin and mineral supplementation and adequate fibre and protein intake). Alongside exercise, these interventions may help optimise nutritional status, minimise muscle loss and improve overall health.