# Obesity in Type 1 Diabetes: Moving Beyond the “Lean” Disease Paradigm to Understand Risk, Complications, and Treatment

**Authors:** Anastasios Tentolouris, Theocharis Koufakis, Evangelos Fousteris

PMC · DOI: 10.1007/s13679-026-00693-9 · 2026-02-21

## TL;DR

Obesity is becoming more common in people with type 1 diabetes, leading to worse health outcomes and complications, and new treatments are being explored to manage this issue.

## Contribution

This review highlights the growing prevalence of obesity in type 1 diabetes and evaluates the risks and treatment options specific to this population.

## Key findings

- Obesity in type 1 diabetes is linked to worse glycemic control and higher risks of complications like heart disease and kidney disease.
- Lifestyle changes and medications like liraglutide and semaglutide show promise for weight loss but carry risks such as hypoglycemia and ketosis.
- Bariatric surgery leads to significant weight loss but offers only modest glycemic benefits and poses metabolic risks.

## Abstract

Overweight and obesity are increasingly common in people with type 1 diabetes mellitus (T1DM). This narrative review synthesizes current evidence on the epidemiology and mechanisms linking excess adiposity with T1DM, the obesity-associated burden of complications, and approaches to obesity management in this population.

Excess adiposity is now frequent in people with T1DM, approaching general-population prevalence, and obesity may also increase the risk of incident T1DM. In T1DM, weight gain reflects intersecting drivers, including intensive insulin therapy, hypoglycemia-related compensatory intake and activity avoidance, obesity-related insulin resistance, and overlapping genetic/hormonal determinants. Across multiple cohorts, higher adiposity is associated with poorer glycemic control and increased risk of cardiovascular events and mortality, as well as higher risks of retinopathy, diabetic kidney disease, and neuropathy. Evidence to guide treatment in T1DM remains limited. Lifestyle approaches require individualization to minimize hypoglycemia and ketosis. RCTs of adjunct liraglutide demonstrate weight loss and insulin-sparing effects but signal dose-dependent risks of hypoglycemia and ketosis. Early RCTs with semaglutide and tirzepatide suggest substantial weight loss and improved glycemic metrics in selected settings, with vigilance for ketosis. Sodium-glucose cotransporter-2 inhibitors have shown modest HbA1c reductions with small but clinically meaningful weight loss in T1DM; however, they are associated with an increased risk of diabetic ketoacidosis. Bariatric surgery yields large weight loss but only modest glycemic benefit and carries risk of metabolic instability.

Obesity is a common, clinically important comorbidity in T1DM, linked to poorer glycemic outcomes and complications. Longer-term, T1DM-specific RCTs are needed to guide weight management and define the benefit-risk of emerging therapies.

## Linked entities

- **Chemicals:** liraglutide (PubChem CID 16134956), semaglutide (PubChem CID 56843331), tirzepatide (PubChem CID 163285897)
- **Diseases:** type 1 diabetes mellitus (MONDO:0005147), retinopathy (MONDO:0005283), diabetic kidney disease (MONDO:0005016), neuropathy (MONDO:0005244), diabetic ketoacidosis (MONDO:0012819)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, IAPP (islet amyloid polypeptide) [NCBI Gene 3375] {aka DAP, IAP}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, GH1 (growth hormone 1) [NCBI Gene 2688] {aka GH, GH-N, GHB5, GHN, IGHD1A, IGHD1B}, FTO (FTO alpha-ketoglutarate dependent dioxygenase) [NCBI Gene 79068] {aka ALKBH9, BMIQ14, GDFD, IFEX9}, TCF7L2 (transcription factor 7 like 2) [NCBI Gene 6934] {aka TCF-4, TCF4}
- **Diseases:** proliferative diabetic retinopathy (OMIM:603933), beta-cell failure (MESH:D051437), Hypoglycemia (MESH:D007003), CV disease (MESH:D002318), NAFLD (MESH:D065626), Gastrointestinal adverse effects (MESH:D005767), Diabetes (MESH:D003920), diabetic retinopathy (MESH:D003930), lactic acidosis (MESH:D000140), Vascular dysfunction (MESH:D002561), bone health (MESH:D001847), TDD (MESH:D020773), Weight loss (MESH:D015431), neuropathic complications (MESH:D002493), osteoporosis (MESH:D010024), DM (MESH:D009223), CKD (MESH:D051436), acidosis (MESH:D000138), Insulin resistance (MESH:D007333), excess (MESH:D006970), MASLD (MESH:D008107), sarcopenia (MESH:D055948), inflammation (MESH:D007249), fibrosis (MESH:D005355), metabolic syndrome (MESH:D024821), albuminuria (MESH:D000419), hyperglycemia (MESH:D006943), hypertension (MESH:D006973), fracture (MESH:D050723), deaths (MESH:D003643), dyslipidemia (MESH:D050171), diabetic complications (MESH:D048909), hyperinsulinemic (MESH:D044903), upper-limb fractures (MESH:D038062), hyperinsulinemia (MESH:D006946), hip fractures (MESH:D006620), mitochondrial dysfunction (MESH:D028361), Diabetic Kidney Disease (MESH:D003928), metabolic dysfunction (MESH:D008659), renal vascular (MESH:D006030), ketosis (MESH:D007662), hypoglycemic (MESH:C000721848), functional impairment (MESH:D003072), Neuropathy (MESH:D009422), Fat mass loss (MESH:C536030), chronic (MESH:D002908), vomiting (MESH:D014839), frailty (MESH:D000073496), peripheral arterial disease (MESH:D058729), Steatosis (MESH:D005234), type 2 diabetes (MESH:D003924), adipose gain (MESH:D015430), heart failure (MESH:D006333), neuropathic (MESH:D009437), nausea (MESH:D009325), Obesity (MESH:D009765), Excess adiposity (MESH:D018205), dysautonomia (MESH:D054969), CAN (MESH:D007674), ankle fractures (MESH:D064386)
- **Chemicals:** vitamin K (MESH:D014812), bupropion (MESH:D016642), Naltrexone (MESH:D009271), ketone (MESH:D007659), dapagliflozin (MESH:C529054), fatty acids (MESH:D005227), carbohydrate (MESH:D002241), EVIDoa2500173 (-), Orlistat (MESH:D000077403), alcohol (MESH:D000438), glucose (MESH:D005947), creatinine (MESH:D003404), blood glucose (MESH:D001786), RA (MESH:D011883), Sotagliflozin (MESH:C575681), Metformin (MESH:D008687), NEFA (MESH:D005230), lipids (MESH:D008055), glycogen (MESH:D006003), Empagliflozin (MESH:C570240)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12923423/full.md

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Source: https://tomesphere.com/paper/PMC12923423