(P22-043-25) Weight Loss in Patients With Treated Type Two Diabetes, Diabetic Nephropathy, Hypertension, and Metabolic-Associated Steatohepatitis: A Randomized Clinical Trial

Objectives: To evaluate the fast weight loss method (very low calorie restriction diet, VLCD) on glycemic profile, renal and liver function, blood pressure (BP), lipid in treated patients with type two diabetes (T2D), diabetic nephropathy with moderate renal failure (DN), hypertension (H), and metabolic-associated steatohepatitis (MASH).

Methods: A 16-week controlled randomized clinical trial including 32 patients aged 30-65 years (17 women) with T2D+DN+H+MASH: 18 in Main (VLCD on Analimentary detoxication); 14 in Controls (symptomatic medicines including empagliflozin). Both groups at baseline received conventional anti-diabetic, anti-hypertensive, symptomatic drugs. Primary endpoints: HbA1c, BP, glomerular filtration (GF), creatinine blood, NAFLD Fibrosis Score (NFS) and Liver Stiffness Measurement (LSM) using FibroScan®. Secondary endpoints: weight loss, hepatic enzymes (ALT, AST, GGT, ALP), lipids.

Results: At 16 weeks, patients in Main weight lost between –14.8 kg (-16%, P < 0.001); their BMI (–6.9 kg/m², P < 0.001) and waist circumference (–18.5 cm, P < 0.001) decreased compared to Control. Changes in Main vs Controls at 16 weeks: fasting glucose (–6.7 ml/min, P=0.0024), HbA1c (–5.3%, P < 0.001), immunoassay insulin (–8.2 μU/mL, P < 0.001), GF (+17 ml/min, P=0.003), systolic/diastolic BP (–22.7/–16.5 mmHg, P < 0.0001), creatinine (–27.3 mmol/l, P=0.008), ALT (–87.2, P < 0.001), AST (–98.4, P < 0.001), cholesterol (–3.2 mmol/l, P=0.002), triglyceride (–1.8 mmol/l, P=0.002), HDL (+1.2 mmol/l, P=0.003), NFS-score (–68.7%, P < 0.001), LSM (–136.9%, P < 0.001). In Controls HbA1c, GF, creatinine, ALT-AST levels did not achieve normal (P>0.025). The fast weight loss method in Main led to adequately decrease in doses of symptomatic medicines up to their complete abolition. In Controls, hyperglycemia, BP and hyperuricemia were difficult to control due to DN and MASH; three patients required intensive care in emergency room.

Conclusions: The fast weight loss method is useful in improving glycemic profiles, renal and liver parameters, BP, lipids, steatosis/fibrosis outcomes in patients with treated T2D+DN+H+MASH. The method allowed patients to stop taking medications.

Funding Sources: Ministry of Science and Higher Education of the Republic of Kazakhstan (Grant for 2024-2026, AP23488544). ClinicalTrials.gov NCT06410352