Case Report: Tirzepatide improves glycemic control in Rabson-Mendenhall syndrome.

BACKGROUND: Rabson-Mendenhall syndrome (RMS) is an extremely rare autosomal recessive disorder caused by variants in the INSR gene, which encodes the insulin receptor. The condition is characterized by profound insulin resistance, resulting in diabetes that is exceptionally difficult to control and carrying a poor prognosis, typically in the second to third decade of life. Death most commonly occurs due to ketoacidosis and severe infections. There is no established consensus on optimal treatment; initial therapy usually includes metformin and pioglitazone, often combined with SGLT2 inhibitors, followed by maintenance with high doses of insulin.

CASE PRESENTATION: Two patients with genetically confirmed RMS were treated with subcutaneous tirzepatide for 3 months (2.5-3.3 mg weekly), followed by a 3-month washout period. Clinical, biochemical, and body composition parameters were assessed at baseline, after treatment, and after withdrawal. After 3 months of treatment, HbA1c decreased from 8.9% to 6.3% in one patient and from 10.3% to 8.1% in the other. Insulin resistance improved in one case, whereas insulinemia decreased markedly in the other. Glycemic control deteriorated after treatment withdrawal. Tirzepatide was generally well tolerated, although both patients experienced a reduction in fat mass, and one developed proliferative retinopathy, probably related to the rapid fall in HbA1c.

CONCLUSIONS: Low-dose tirzepatide improved glycemic control in RMS and may represent a potential adjunctive therapy, warranting careful monitoring.