Effect of pegvisomant on glucose metabolism

S Aznar; E Boix; P Revert; O Moreno; A López-Maciá; A Picó

Aim: To quantify the effect of pegvisomant on glucose homeostasis, lipid profile and disease activity in acromegaly.

Methods: 5 Patients with active acromegaly after surgery, radiotherapy and somatostatin analogs were included. Somatostatin analogs were withdrawn 6 weeks before starting pegvisomant and it was initially administered subcutaneously at doses of 10 mg daily. Doses were progressively increased every 3 to 4 weeks until IGF1 normalization. Glucose homeostasis (fasting glucose, HbA1c, HOMA), lipid profile and biochemical disease activity (IGF1, GH, IGFBP3) were assessed basally and at 3, 6 and 12 months after starting pegvisomant. Vital signs and ring size measurements were also assessed at each visit. Quality of life measured by AcroQol and tumor volume determined by MRI were evaluated basally and after one year of treatment. Non-parametrical tests were used to study statistical significance.

Results: 5 patients (3 males) with a median of 49 years of age were included. Previous surgery had been perfomed in all of them and postoperative radiotherapy in four of them. Three patients were diabetic. Median dose of pegvisomant required to normalize IGF1 levels was 20 mg daily. Diabetic patients showed a median reduction of HbA1c of 0.5% after one year of treatment. There were trends toward improvements in HOMA, fasting glucose, blood pressure, total cholesterol, LDL cholesterol, ring size measurement and quality of life, although statistical significance was not reached. As expected IGF1 decreased significantly.

Table 1
months	IGF-1 (ng/ml)	HbA1c (%)	Glucosa (mg/dl)	HOMA
Basal	910(p25 615–p75 1219)	6 (p25 4.9–p75 7.7)	143(p25 104–p75 160)	3.57(p25 1.96–p75 5.25)
3	601(p25 376–p75 934)*	5.6 (p25 4.4–p75 7.9)	101(p35 98–p75 198)	3.57(p25 2.2–p75 4.3)
6	540(p25 456–p75 756)*	6 (p25 4.6–p75 7.8)	108(p25 103–p75 164)	3.52(p25 0.5–p75 4.9)
12	416(p25 319–p75 651)*	6 (p25 4.45–p75 7.15)	93(p25 88.5–p75 146.5)	2.98(p25 1.65–p75 4.66)

Conclusions: Pegvisomant shows a beneficial effect on glucose metabolism reducing insulin resistance, fasting plasma glucose and HbA1c. It could also reduce blood pressure and total and LDL cholesterol. Through these effects the drug might contribute to reduce cardiovascular events in acromegaly.

Endocrine Abstracts

P609