Year in Review: Endocrinology 2019

JAGDEESH ULLAL, M.D., M.S.

CLINICAL ASSOCIATE PROFESSOR OF MEDICINE

UPMC CENTER FOR DIABETES AND ENDOCRINOLOGY

DIVISION OF ENDOCRINOLOGY AND METABOLISM

OCTOBER 11TH, 2019

Disclosures

u No Relevant disclosure or conflicts of interest

Objectives

u Diabetes updates

v Epidemiology

v Cardiovascular outcomes trials

v Newer agents and approvals

v Diabetes Technology

u Thyroid updates

u Metabolic Bone disease updates

u Obesity

Diabetes Type 1 and Type 2

Diabetes Trends

Nathan et al (2019) Diabetologia DOI 10.1007/s00125-019-4928-8 © Springer-Verlag GmbH Germany, part of Springer Nature 2019

HbA1c levels, measured annually over time in DPP/DPPOS in all participants based on original intention-to-treat assignments

Silvio E. Inzucchi, MD et. al. Diabetes Care 2012 Jun; 35(6): 1364-1379.

Framework for Considering Overall Health and Patient Values in Determining Clinical Targets in Adults Aged ≥ 65 y

LeRoith D et al J Clin Endocrinol Metab 104:1520, 2019

Completed and Ongoing Cardiovascular Outcomes Trials

Cefalu WT et al. Diabetes Care 2018;41:14-31©2018 by American Diabetes Association

Cardiovascular Outcome Trials with GLP-1 Receptor Agonists

Oral Semaglutide

u 3 mg, 7 mg, 14 mg oral

u Take on an empty stomach, ½ hour before food

u Use half cup of water to take medication

The Ominous Octet: Describing The Eight Pathophysiologic Defects in Diabetes that

contribute to Hyperglycemia

DeFronzo RA. Diabetes. 2009;58:773-795.

Ewan R. Pearson (2019) Diabetologia DOI 10.1007/s00125-019-4909-yAdapted from McCarthy MI (2017) Diabetologia, under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)

Deconvoluting the diabetes component pathways

https://www.diabetesgenes.org/mody-probability-calculator/

Diagnosis of LADA

Pieralice S, Pozzilli P. Latent Autoimmune Diabetes in Adults: A Review on Clinical Implications and Management. Diabetes Metab J. 2018;42(6):451–464. doi:10.4093/dmj.2018.0190

Sodium Glucose Transporter Inhibitors (SGLT2i)

27

dapagliflozin , canagliflozin, empagliflozin, ertugliflozin

Efficacy Intermediate (Reduce A1C by ~ 0.8-1.0%)

Risk for hypoglycemia

Do not cause hypoglycemia when used alone or in combination with metformin

Weight Weight loss

Side effects Genito-urinary infectionsDehydrationAmputations (canagliflozin)Fracture risk (canagliflozin)

Cost High

Associated with reductions in hospitalizations for HF, weight loss, reductions in BP, progression of renal disease and CVD events

Empagliflozin associated with reduced CVD and all cause mortality

CVDDeath

All Cause

Mortality

NonfatalMI

Nonfatal CVA

Renal Outcomes

Empagliflozin(EMPA-REG)

38% 32% NSD NSD 39%

Canagliflozin(CANVAS,CREDENCE)

20% NSD NSD 40%

Dapagliflozin(DECLARE)

NSD NSD NSD NSD 24%

All SGLT2i agents were associated with significant reductions in hospitalizations for heart failure

Summary Table: CVOT with SGLT2i

Disadvantages:

ü Increase in risk for “euglycemic DKA”

ü High risk for volume depletion, hypotension and dehydration

ü Use carefully in the elderly or those receiving diuretics

ü Contraindicated in patients with advanced kidney disease

ü Increase in fracture risk observed with canagliflozin

ü Increase risk of amputations observed with canagliflozin

ü Post-marketing reports of acute kidney injury (cana, dapa)

ü Personal note: Use with caution in men with prostatic hyperplasia

ü Cost! (30 tablets empa $476 / cana $498 / dapagliflozin $485)

Sodium Glucose Transporter (SGLT) 2 Inhibitors

SD Wiviott et al. N Engl J Med 2019;380:347-357.

Dapagliflozin: Major Cardiovascular and Renal Outcomes and Death from Any Cause.

June 4, 2019

FDA Adverse Event Reporting System (FAERS) database Report of 55 cases of patients receiving SGLT2i from 5 days – 49 months

Age 33-87: 39 men / 16 women

Comparator: FDA reports 19 cases associated with other DM agents 1984-2019:

• 8 treated with metformin

• 8 treated with insulin

• 2 treated with sitagliptin + metformin

• 1 treated with dulaglutide

Bowes et al (2019) Diabetologia DOI 10.1007/s00125-019-4958-2 © Springer-Verlag GmbH Germany, part of Springer Nature 2019

Heart failure (HF) outcomes with select glucose-lowering therapies

Diabetes Technology

Home Glucose Testing enters a new era…

From this:

To this:

Diabetes TechnologyFlash Continuous Glucose Monitoring Systems

Freestyle Libre®

u Introduced 2014u Does not require calibration with FS BGu Minimally invasive

u Sensors last 10-14 days

u Does not alarm for high or low BGu Reports BG only when holding the “reader” up to

the sensoru Connects with Smart Phones

Criteria:• The patient is receiving ≥ 3 daily insulin injections (MDI) or uses

an insulin infusion pump

• There is documentation of 30 days of home blood glucose monitoring ≥ 4 times a day

• There is a need for frequent adjustments by the patient on the basis of therapeutic testing results.

https://www.medicare.gov/Pubs/pdf/11022-Medicare-Diabetes-Coverage.pdf (accessed 11-19-2018)

Implanted Continuous Glucose Sensor (Eversense)

Requires minor surgical procedure for implantation and removal

Diabetes Technology

I Sim. N Engl J Med 2019;381:956-968.

Integration of Sensor, Smartphone, and Electronic Health Record (EHR) Data for Patients and Clinicians.

Data Flow of Wearable Sensors and the Internet of Things.

Thyroid

UPMC Center for Diabetes and EndocrinologyThyroid Biopsy Unit

Esra Karslioglu-French, MD*

Elena Morariu, MD* Pooja Manroa, MD, ECNU*

Jagdeesh Ullal, MD, ECNU*

ECNU is a professional certification through the American College of Endocrinology in the field of neck ultrasonography for physicians who perform consultations and diagnostic evaluations for thyroid and parathyroid disorders through both diagnostic ultrasound and ultrasound-guided fine needle aspiration (UGFNA)

Hyperthyroidism

Kitahara CM, Berrington de Gonzalez A, Bouville A, et al. Association of Radioactive Iodine Treatment With Cancer Mortality in Patients With Hyperthyroidism. JAMA Intern Med. Published online July 01, 2019179(8):1034–1042. doi:10.1001/jamainternmed.2019.0981

HB Burch. N Engl J Med 2019;381:749-761.

Classification of Drug Effects on the Thyroid.*

Immune-Related Adverse Events Associated with Immune Checkpoint Blockade

Immune checkpoint blockade can result in inflammation of any organ. Shown are the most common immune-related adverse events that clinicians encounter in patients treated with immune checkpoint blockade.

Michael A. Postow, M.D. et.al.N Engl J Med 2018; 378:158-168

Fig 1

Journal of the American College of Radiology 2017 14, 587-595DOI: (10.1016/j.jacr.2017.01.046)

TI-RADs for Thyroid Nodules

Metabolic Bone Diseases

AG Pittas et al. N Engl J Med 2019;381:520-530.

Kaplan–Meier Curves for Survival Free from Diabetes among Adults at Risk for Type 2 Diabetes with 4000 IU of Vitamin D3 daily

Proton Pump Inhibitors and Fractures

u 24 observational studies with 2,103,800 participants (319,568 hip fracture patients)

u Patients with PPIs had a greater risk of hip fracture than those without PPI therapy (RR1.20, 95% CI 1.14–1.28, p < 0.0001).

u Exercise caution when considering a long-term PPI treatment for patients who already have an elevated risk of hip fracture.

Romozozumab

u Monoclonal antibody romosozumab to treat osteoporosis in postmenopausal women at high risk for fracture, according to a press release from the agency.

u 245 subjects (163 romosozumab, 82 placebo), at month 12, the mean percentage change from baseline in the LS and TH BMD was significantly greater for the romosozumab group than for the placebo group

u Treatment with romosozumab for 12 months increased the spine and hip BMD compared with placebo and was well tolerated in men with osteoporosis

u May increase the risk of heart attack, stroke and cardiovascular death, so it’s important to carefully select patients for this therapy

Endocrine Society Guidelines for Management of Postmenopausal Osteoporosis

Richard Eastell, Clifford J Rosen, Dennis M Black, Angela M Cheung, M Hassan Murad, Dolores Shoback, Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 104, Issue 5, May 2019, Pages 1595–1622

Statin use and Bone Health

u Older women were included in a population-based study of 3028 women (mean age 77.8 ±1.6 years)

u Bone geometry and microstructure were measured at the ultra-distal and distal (14%) site of radius and tibia using high-resolution peripheral quantitative computed tomography

u Use of statins was associated with better cortical bone characteristics in older women

Obesity and Bariatrics

Bariatric surgery

u A large base of research indicates that bariatric surgeries such as Roux-en-Y-gastric bypass (RYGB), vertical sleeve gastrectomy (VSG), and biliopancreatic diversion (BPD) improve diabetes in most patients, with effects frequently evident prior to substantial weight reduction.

u Efficacy of surgery is superior to intensive life-style/medical management.

u The improvement of insulin sensitivity that occurs with weight loss (e.g. the result of diet, illness, physical training) also accompanies bariatric surgery.

u However, there is evidence to support specific effects of surgery on insulin clearance, hepatic glucose production, and islet function. Understanding the mechanisms by which surgery affects these parameters of glucose regulation has the potential to identify new targets for therapeutic discovery.

The effects of bariatric surgery on islet function, insulin secretion, & glucose control Jonathan D Douros, Jenny Tong, David A D'Alessio Endocrine Reviews 2019 June 26

TH Inge et al. N Engl J Med 2019;380:2136-2145.

Weight Change and Remission of Diabetes and Hypertension during the 5-Year Period after Gastric Bypass Surgery.

Five-Year Outcomes of Gastric Bypass in Adolescents as Compared with Adults

Thank you

QUESTIONS