1. Mastery of Medicine in Diabetes Management Video Roundtable

2. Part I: Cardiovascular Disease and Diabetes
Moderator:
David M. Nathan, MD
Panelists:
Carol J. Levy, MD, CDE
Anne L. Peters, MD

3. Slide 1. Prediction of Cardiovascular Events in Type 2 Diabetes by Means of a Genetic Risk Score1
N = 5360 self-reported white subjects with type 2 diabetes
Genetic risk score: derived by adding the effect size-weighted number of risk alleles at 40 cardiovascular disease loci previously identified within the general population
Scores ranged from 27 to 62
Each unit increase associated with a 3% additional risk of a major adverse cardiovascular event (OR 1.03, P = .002)
Effect attenuated by adjustment for clinical predictors (OR 1.42)
Addition of genetic risk profile to clinical risk score led to 9% increase in the ability to correctly reclassify individuals with major adverse cardiovascular events, and 4% increase in the ability to correctly reclassify individuals with nonevents
Morieri M, et al. American Diabetes Association 77th Scientific Session: Presentation 2-OR/2.

4. Slide 2. All-Cause Mortality in Randomized Controlled Trials of Type 2 Diabetes2
33 randomized, controlled trials: 175,310 patients and 693,665 patient-years of follow-up
Advanced chronic kidney disease associated with highest mortality rates
Barkoudah E, et al. American Diabetes Association 77th Scientific Session: Presentation 427-P.

5. Slide 3. DEFENCE Study3
16 week multicenter, prospective, open-label, randomized parallel study
Type 2 diabetic patients randomized to
750 mg metformin + 5 mg dapagliflozin
1500 mg metformin
Results
Flow-mediated dilation (marker of vascular endothelial function): comparable between groups, although with a trend favoring dapagliflozin
Hemoglobin A1c, fasting plasma glucose, plasma glucagon, and body weight significantly decreased in both groups
Urine 8-OHdG (biomarker of oxidative stress) significantly decreased with dapagliflozin compared with metformin alone
Shigiyama F, et al. American Diabetes Association 77th Scientific Session: Presentation 12-LB.

6. Slide 4. EMPA-REG OUTCOME Trial4,5
Patients with type 2 diabetes and established cardiovascular disease randomized to receive standard of care plus
Empagliflozin 10 mg or 25 mg
Placebo
All study endpoints adjusted for control of blood pressure (systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg), LDL-C (<100 mg/dL), and hemoglobin A1c (<7.5%)
Results
HR for hospitalizations for heart failure:
33%-36% reduction in hospitalizations for heart failure with empagliflozin
HR for cardiovascular death:
38%-41% reduction in cardiovascular death with empagliflozin
HR for all-cause mortality:
33%-34% reduction in all-cause mortality with empagliflozin
Conclusion
Empagliflozin reduces the risk of hospitalization for heart failure, cardiovascular death, and all-cause mortality even when analyses are adjusted for control of blood pressure, LDL-C, and hemoglobin A1c, suggesting that the risk reduction with empagliflozin is irrespective of these conventional risk factors
Zinman B, et al. American Diabetes Association 77th Scientific Session: Presentation 1173-P.
Fitchett D, et al. American Diabetes Association 77th Scientific Session: Presentation 1172-P.

7. Part II: GLP-1 Receptor Agonists
Moderator:
David M. Nathan, MD
Panelists:
Carol J. Levy, MD, CDE
Anne L. Peters, MD

8. Slide 5. Changes in Insulin Dosing Induced by Adding Liraglutide6
26-week randomized, placebo-controlled trial
44 overweight C-peptide negative adults with insulin-pump treated type 1 diabetes and suboptimal glycemic control
1.8 mg liraglutide vs placebo
RESULTS
Liraglutide significantly reduced hemoglobin A1c compared with placebo (-0.6% vs 0.2%, P <.001)
Liraglutide significantly reduced body weight compared with placebo (-6.4 kg vs -0.6 kg, P <.001)
Basal/bolus insulin distributions similar between 2 groups
Daily carbohydrate intake constant in both groups
Insulin:carbohydrate intake ratios increased significantly at mid-day and evening hours in the liraglutide group compared with the placebo group (P <.05)
Insulin:carbohydrate intake ratio in the morning was unchanged between the 2 groups
Schmidt S, et al. American Diabetes Association 77th Scientific Session: Presentation 72-OR.

9. Slide 6. DUAL VII Trial8 26-week open-label trial
506 patients with type 2 diabetes uncontrolled on metformin and U insulin glargine U100
Insulin degludec + liraglutide vs basal-bolus (insulin glargine U100 + insulin aspart up to 4 times per day)
RESULTS
Mean hemoglobin A1c decreased from 8.2% to 6.7% in both arms, confirming noninferiority of insulin degludec + liraglutide
A similar proportion of patients in each arm achieved hemoglobin A1c targets
Total daily insulin dose lower with insulin degludec + liraglutide (40.4 U vs 84.1 U, P <.0001)
Body weight decreased with insulin degludec + liraglutide and increased with basal-bolus treatment
Rate of hypoglycemic episodes was lower with insulin degludec + liraglutide (P <.0001)
Billings LK, et al. American Diabetes Association 77th Scientific Session: Presentation 136-OR.

10. Part III: New Insulin Therapies in Diabetes
Moderator:
David M. Nathan, MD
Panelists:
Carol J. Levy, MD, CDE
Anne L. Peters, MD

11. Slide 7. Potential Uses for Ultra-Rapid Insulins
Pediatric patients
Geriatric patients
Artificial pancreas systems
Patients with type 1 diabetes and poor insulin control in the morning (breakfast)

12. Slide 8. Insulin Glargine U300 vs Insulin Degludec9
Comparison of steady-state pharmacokinetic and pharmacodynamic profiles
Insulin glargine U300 (0.4 and 0.6 U/kg/day)
Insulin degludec (0.4 and 0.6 U/kg/day)
Primary endpoint: within-day variability of smoothed glucose infusion rate of 24-hour dosing period
20% lower with glargine U300 or than with degludec 0.4 U/kg/day (P = .047) but similar to degludec 0.6 U/kg/day
Other endpoints
Relative degree of serum insulin concentration 24-hour fluctuation
13% lower with glargine U300 than with degludec 0.4 U/kg/day
17% lower with glargine U300 than with degludec 0.6 U/kg/day
Area under the INS time curve
Distribution more even with glargine than both doses of degludec
Bailey TS, et al. American Diabetes Association 77th Scientific Session: Presentation 985-P.

13. Slide 9. SWITCH 1 and 2 Trials10
64-week, double-blind, treat-to-target cross-over trials
Type 1 diabetes (SWITCH 1)
Type 2 diabetes (SWITCH 2)
Insulin degludec once daily vs Insulin glargine U100 once daily
Hemoglobin A1c noninferiority confirmed in both trials
Reduction in hypoglycemia
Significant reductions across all definitions of hypoglycemia with degludec vs glargine U100 in SWITCH 1
Significant reductions with degludec vs glargine U100 in SWITCH 2 in most definitions of hypoglycemia, except severe hypoglycemia
Wysham CH, et al. American Diabetes Association 77th Scientific Session: Presentation 974-P.