Impact of SGLT2 on Glucosuria in HNF1A-MODY (MOD3ST-CLAMP)

Steno Diabetes Centers

Status: Completed

Conditions: Maturity-Onset Diabetes of the Young, Type 3; Type 2 Diabetes

Treatments: Other: Hyperglycaemic clamp; Drug: Empagliflozin; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05417646

H-21066984

Details and patient eligibility

About

Maturity onset diabetes of the young (MODY) is a subtype of diabetes which is caused by mutations in specific genes leading to diabetes. The most common cause of MODY is due to mutations in the gene hepatocyte nuclear factor 1 alpha (HNF1A) and is consequently named HNF1A-MODY (or MODY3). HNF1A-MODY is associated with urinary excretion of glucose at lower blood glucose levels compared to other types of diabetes. Normally, glucose is reabsorbed by sodium-glucose cotransporter 2 (SGLT2), but SGLT2 is downregulated due to the mutation in HNF1A. Investigators aim to evaluate the impact of the decreased expression of SGLT2 on glucosuria in patients with HNF1A-MODY compared to patients with type 2 diabetes (T2D) using a single dose of an SGLT2 inhibitor during a glucose clamp experiment.

Full description

Participants: Patients with HNF1A-MODY (n=12) and patients with T2D (n=12)

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥18 years
• HNF1A-MODY verified by genetic testing (only patients with HNF1A-MODY)
• Type 2 diabetes diagnosis according to World Health Organization (only patients with type 2 diabetes)
• Treatment with diet and/or a glucose-lowering drug (only patients with HNF1A-MODY)
• Normal haemoglobin (males 8.3-10.5 mmol/l, females 7.3-9.5 mmol/l)
• Informed consent

Exclusion criteria

• Nephropathy (estimated GFR <60 ml/min/1.73m2 and/or albuminuria)
• Known significant liver disease and/or plasma alanine aminotransferase (ALT) and/or plasma aspartate aminotransferase (AST) above 2 × normal values)
• Pregnancy or breastfeeding
• Treatment with SGLT2 inhibitor
• Fasting plasma glucose > 10 mmol/l
• Family history of HNF1A-MODY (only patients with type 2 diabetes)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

21 participants in 4 patient groups, including a placebo group

HNF1A-MODY - SGLT2 inhibition

Active Comparator group

Description:

3-hour hyperglycemic clamp with inhibition of SGLT2 (single-dose empagliflozin 25 mg two hours before clamp)

Treatment:

Drug: Empagliflozin

Other: Hyperglycaemic clamp

HNF1A-MODY - Placebo

Placebo Comparator group

Description:

3-hour hyperglycemic clamp without inhibition of SGLT2 (placebo comparator to empagliflozin)

Treatment:

Drug: Placebo

Other: Hyperglycaemic clamp

Type 2 Diabetes - SGLT2 inhibition

Active Comparator group

Description:

3-hour hyperglycemic clamp with inhibition of SGLT2 (single-dose empagliflozin 25 mg two hours before clamp)

Treatment:

Drug: Empagliflozin

Other: Hyperglycaemic clamp

Type 2 Diabetes - Placebo

Placebo Comparator group

Description:

3-hour hyperglycemic clamp without inhibition of SGLT2 (placebo comparator to empagliflozin)

Treatment:

Drug: Placebo

Other: Hyperglycaemic clamp