Body Mass Index As One of Determinants of Biochemical Control in Acromegaly: 2-Year Data from the Soda Registry

Presentation Number: SUN 449
Date of Presentation: April 2nd, 2017

Murray B. Gordon*1, Mark E Molitch2, Whitney W. Woodmansee3, Adriana Gabriela Ioachimescu4, Olga V. Gambetti5, Don Carver6, Beloo Mirakhur7, David Cox8 and Roberto Salvatori9
1Allegheny General Hospital, Pittsburgh, PA, 2Northwestern University, Chicago, IL, 3Mayo Clinic, Jacksonville, FL, 4Emory University School of Medicine, Atlanta, GA, 5Ipsen Biopharmaceuticals, Basking Ridge, NJ, 6Ipsen Biopharmaceuticals, Sedona, AZ, 7Ipsen Biopharmaceuticals, Inc., Basking Ridge, NJ, 8Ipsen Biopharmaceuticals, Inc., 9Johns Hopkins University, Baltimore, MD

Abstract

Background: Body mass index (BMI), along with age and hypertension, is considered a significant risk factor for type 2 diabetes (DM) in acromegaly as it is in the general population1.This report examined 2-year biochemical efficacy among patients with and without obesity from the SODA registry, a multi-center, open-label, observational study of long-acting somatostatin analog lanreotide depot (LAN) for acromegaly treatment.

Methods: Demographics, previous acromegaly therapy, and clinical and biochemical data were collected in patients at enrollment, Month 12 (M12) and Month 24 (M24). The groups with BMI<30 kg/m2 (non-obese) and BMI≥30 kg/m2 (obese) were analyzed. Student' t-test, Chi-square and Fisher's exact test were used for exploratory statistical analyses.

Results: Among 235/241 patients with available BMI at enrollment, 139 (59.1%) had BMI≥30 (mean, 36.4±6.0) and 96 (40.9%) had BMI<30 (mean, 26.5±2.5).The obese group was younger (47.4±13.0 vs 53.5±15.5 years, p=0.001), and more often used pegvisomant prior to enrollment (21.6% vs 9.4%, p=0.047). No differences between groups in gender distribution, tumor size, arterial hypertension, statin use, prior surgery and radiation were revealed. Similarly, BMI<30 and BMI≥30 groups did not differ in the proportion of IGF-I-controlled (IGF-I<ULN) patients (52.0% vs 43.5%), mean HbA1c levels (6.6±1.9 vs 6.4±1.6) and proportions of patients with HbA1c <5.7%, 5.7%–6.4%, and ≥6.5%. Patients with DM, comprising 25.3% of the SODA cohort, had a greater BMI vs non-DM (34.3±7.2 vs 31.7±6.7, p=0.013). During LAN therapy, both BMI≥30 and BMI<30 groups demonstrated increases in the proportions of IGF-I controlled patients at M12 and M24 vs enrollment (p<0.05). However, a significantly lower proportion of BMI≥30 compared with BMI<30 group achieved IGF-I<ULN at M24 (62.8% vs 91.4%, p=0.003), with no difference at M12 (68.5% vs 77.3%, p>0.05). Conversely, higher proportions of BMI≥30 vs BMI<30 patients achieved GH<1.0 ng/ml both at M12 (74.4% vs 46.2%, p=0.02) and M24 (70.0% vs 38.9%, p=0.03). A similar pattern, although non-significant, was observed for GH£2.5 ng/ml at M12 (87.2% vs 76.9%) and M24 (86.7% vs 66.7%).

Conclusions: Our data indicates a higher rate of IGF-I normalization in non-obese vs obese patients treated with lanreotide depot. One likely explanation is the hyperinsulinism in the obese group which enhanced synthesis of IGF-I through upregulation of hepatic GH receptors.2,3 The discordance in normalization of IGF-I and GH in obese acromegaly patients may also be explained by hyperinsulinism both increasing hepatic GH sensitivity4 and increasing free fatty acids which suppress GH release5.

 

Disclosure: MBG: , Novartis Pharmaceuticals, , Corcept. MEM: Ad Hoc Consultant, Abbott Laboratories, Owner, Amgen, Investigator, Bayer, Inc., Investigator, Novartis Pharmaceuticals, Investigator, Novo Nordisk, Investigator, Ipsen, Investigator, Johnson &Johnson, Advisory Group Member, Jansen Pharmaceuticals, Member of advisory committees or review panels, Merck & Co., Member of advisory committees or review panels, Pfizer, Inc.. AGI: Researcher, Novartis Pharmaceuticals, Researcher, Chiasma, Research Support, Researcher, Pfizer, Inc., Consultant, Ionis & Chiasma-Consultant. OVG: Employee, Ipsen. DC: Consultant, Ipsen. BM: Employee, Ipsen. DC: Employee, Ipsen. RS: Advisory Group Member, Novo Nordisk, Ad Hoc Consultant, Pfizer, Inc., Advisory Group Member, ionis. Nothing to Disclose: WWW