Endocrinologist Roper Endocrinology health/health... · 2018-02-20 · glycated albumin or fructosamine level Bergenstal RM, Gal RL, Connor CG, et al. Racial Differences in the Relationship

EndocrinologistRoper Endocrinology

Medical Detection Dog has saved life of owner with type 1 diabetes hundreds of times

▪ Dog has been trained as hypo alert dog

▪ Detect specific odors, including the ability to sense when Patient blood glucose levels are low.

Empagliflozin is SGLT-2 inhibitor Primary Endpoint: MACE

▪ Death from cardiovascular causes

▪ Nonfatal myocardial infarction

▪ Nonfatal stroke

Secondary Endpoint

▪ Hospitalization + Primary Endpoint

Cumulative incidence function. HR, hazard ratio

5

EMPA-REG OUTCOME:

Cardiovascular death

Zinman B et al. N Engl J Med 2015, published on-line, 9-1-15, DOI:10.1056/NEJMoa1504720

HR 0.62

(95% CI 0.49, 0.77)

p=0.0001

N=7020

38%

Cumulative incidence function. HR, hazard ratio

6

N=7020

EMPA-REG OUTCOME:

Hospitalization for heart failure

Zinman B et al. N Engl J Med 2015, published on-line, 9-1-15, DOI:10.1056/NEJMoa1504720

HR 0.65

(95% CI 0.50, 0.85)

p=0.001735%

Taken from http://www.nephjc.com/news/2016/6/23/empa-reg-renal-resultsWanner, Christoph, et al. "Empagliflozin and progression of kidney disease in type 2

diabetes." New England Journal of Medicine 375.4 (2016): 323-334.

http://www.nephjc.com/news/2016/6/23/empa-reg-renal-results

Taken From ADA 77th session - The Integrated results o f CANVAS ProgramNeal, Bruce, et al. "Canagliflozin and cardiovascular and renal events in type 2 diabetes." New

England Journal of Medicine377.7 (2017): 644-657.

Patient with type 2 DM

▪ HbA1C>7 < 10.5 %

▪ eGFR>30

▪ Age>30 with history of prior CV event

▪ Age>50 with >2 CV factors

Primary

▪ MACE

Secondary

▪ All cause mortality

▪ CV death

Exploratory

▪ If successful superiority will be tested

▪ Multiple factors

























9,340 patients with type 2 diabetes. The primary composite outcome in the time-to-

event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (MACE)

81% patient have prior CVD Rest were high risk of CVD Long Term therapy duration of DM 12 yrs with

meal HbA1C 8.7. Pancreatitis was lower in Liraglutide group non-

significantly.

Marso, Steven P., et al. "Liraglutide and cardiovascular outcomes in type 2 diabetes." New England Journal of Medicine 375.4 (2016): 311-322.

LEADER trial:Death from Cardiovascular Causes

15

10

20

5

0

0 6 12 18 24 30 36 42 48 54

Placebo

Liraglutide

Pat

ien

ts w

ith

an

eve

nt

(%)

Months since randomization

Hazard ratio, 0.78 (95% CI, 0.66–0.93)P=0.007

Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial

Adapted from: Marso SP et al., NEJM 2016Marso, Steven P., et al. "Liraglutide and cardiovascular outcomes in type 2 diabetes." New England Journal of Medicine 375.4 (2016): 311-322.

LEADER trial:Death from Cardiovascular Causes

15

10

20

5

0

0 6 12 18 24 30 36 42 48 54

Placebo

Liraglutide

Pat

ien

ts w

ith

an

eve

nt

(%)

Months since randomization

Hazard ratio, 0.78 (95% CI, 0.66–0.93)P=0.007

Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial

Adapted from: Marso SP et al., NEJM 2016Marso, Steven P., et al. "Liraglutide and cardiovascular outcomes in type 2 diabetes." New England Journal of Medicine 375.4 (2016): 311-322.

Renal outcome occurred in fewer participants in the Liraglutide group than in the placebo group (P value =0.003)

New onset of persistent macroalbuminuria statically significant 161 vs. 215 patients(P value = 0.004)

.

https://www.uptodate.com/contents/glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-type-2-diabetes-mellitus/abstract/26

Patients with 83% CAD,CKD or both Primary outcome

▪MACE

▪2 yrs

Marso, Steven P., et al. "Semaglutide and cardiovascular outcomes in patients with type 2 diabetes." New England Journal of Medicine (2016).


Retinopathy increased Nephropathy decreased Low incidence of pancreatitis – same as

placebo.

Taken from ADA 77th session Cardiovascular Outcomes with Semaglutide in Subjects with Type 2 Diabetes Mellitus (SUSTAIN 6)

https://webcasts.diabetes.org/netadmin/Preview_redirect.aspx?lid=43748

Taken from ADA 77th session Cardiovascular Outcomes with Semaglutide in Subjects with Type 2 Diabetes Mellitus (SUSTAIN 6)

https://webcasts.diabetes.org/netadmin/Preview_redirect.aspx?lid=43748

1402 patients with type 1 diabetes sotagliflozin (400 mg per day) or placebo for 24

weeks. Primary Endpoints

▪ HbA1C level at 7.0% at week 24

▪ Episodes of severe hypoglycemia or diabetic ketoacidosis after randomization.

Garg, Satish K., et al. "Effects of sotagliflozin added to insulin in patients with type 1 diabetes." New England Journal of Medicine 377.24 (2017): 2337-2348.

Secondary Endpoints

▪ Glycated hemoglobin level

▪ Weight

▪ Systolic blood pressure

▪ Insulin Dosing

Result

▪ HbA1C level < 7 %

▪ 200 of 699 patients [28.6%] vs. 107 of 703 [15.2%], P<0.001


HbA1C level (difference, −0.46 percentage points)

Weight (−2.98 kg) Systolic blood pressure (−3.5 mm Hg) Mean daily bolus dose of insulin (−2.8 units per

day) (P≤0.002 for all comparisons). Hypoglycemia similar rate 3.0% [21 patients]

and 2.4% [17] (placebo) DKA was higher in the sotagliflozin group than

in the placebo group (3.0% [21 patients] and 0.6%


Debate wheatear african American has slightly different HbA1C than Caucasian population.

12 week observational study 104 patient in each arm with type 1 diabetes

for at least 2 years and had an HbA1c level of 6.0% to 12.0%.

Results 9.1% in african American persons and 8.3% in

Caucasian person

Mean glucose level and HbA1C was significantly different P value <0.013.

AA had 0.4% HbA1C level higher for the same level of mean glucose level

No significant difference was found in glycated albumin or fructosamine level

Bergenstal RM, Gal RL, Connor CG, et al. Racial Differences in the Relationship of Glucose Concentrations and Hemoglobin A1c Levels. Ann Intern Med 2017; 167:95.

https://www.uptodate.com/contents/whats-new-in-endocrinology-and-diabetes-mellitus/abstract/14

- 7500 people for 2 yrs – type 2 DM- MACE outcome similar in both groups- Glycemic control is similar- severe and nocturnal hypoglycemia were

lower in patients taking degludec.

Background

▪ Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) account for >95% of bariatric procedure in US

▪ No validated approach to guide procedure selection in type 2 DM

Methods

▪ 659 patients with T2DM who underwent RYGB and SG

Follow-up of 7 years (range 5–12) Diabetes remission (HbA1C <6.5% off

medications) was observed in 49% after RYGB and 28% after SG (P < 0.001).

Type of diabetes (mild, moderate and severe was determined by normogrames)

Mild diabetes –both similar in remission Moderate diabetes- RYBG>SG in remission Severe Diabetes- low rate for both of them.

DPT trial

▪ 339 patients at high risk for type 1 diabetes

▪ Siblings of diabetic patients with high serum islet-cell antibody concentrations

▪ low acute insulin responses to glucose

▪ Randomly assigned to receive close observation or low-dose subcutaneous insulin

▪ 3.7 yrs and similar incidence of diabetes in both arms.

Randomization to receive 7.5 mg/d of oral insulin (n = 283) or placebo (n = 277)

2.7 yrs study Autoantibody group with family history of

type 1 DM Oral insulin at a dose of 7.5 mg/d, compared

with placebo, did not delay or prevent the development of type 1 diabetes over 2.7 years

443 age 10 to 16 yrs Type 1 DM patient with upper 1/3 of albumin/cr ratio

Treated them with ACE-I and Statin therapy Did not show any significant reduction or

difference with ACE-I therapy for progression.

Low CVD risk with long term trial Currently High CVD risk with short term trial Low CVD risk with long period of time and

earlier stage of the disease with issues with compliance and event rates will be lower.

Well designed than can be beneficial Low CVD risk will be long term trials unless

changes in regulation

26 week trial Different oral dosing from 2.5 mg to 40 mg

vs Placebo vs Weekly GLP-1 Agonist therapy Main Outcome:

▪ HbA1C level , side effects Results

▪ HbA1C level oral seminglutide (dosage-dependent range, −0.7% to −1.9%)

▪ Semaglutide (−1.9%)

▪ Placebo (−0.3%)

10-day wear CGM sensor One fingerstick calibration per day Includes a 30% thinner transmitter and

redesigned one-button inserter. Dexcom might choose to skip directly to the

no-calibration G6 – secondary to free style libre.

Might opt to launch the one calibration per day version first (followed by an update)

Apple Watch app 85 per cent accurate in diagnosing diabetes

14000 patient of deepheart technology The heart and pancreas are linked via the

body's nervous system, so when a person starts to develop diabetes their heart pattern changes.

Could accurately detect high cholesterol, high blood pressure and sleep apnea to 74%, 81% and 83% accuracy respectively.

Heart rate with artificial intelligence-based algorithm .

https://www.diabetes.co.uk/body/heart.html

https://www.diabetes.co.uk/body/pancreas-and-diabetes.html

https://www.diabetes.co.uk/body/nervous-system.html

https://www.diabetes.co.uk/sleep-apnea-and-diabetes.html

Bergenstal RM, Gal RL, Connor CG, et al. Racial Differences in the Relationship of Glucose Concentrations and Hemoglobin A1c Levels. Ann Intern Med 2017; 167:95.

Mann JFE, Ørsted DD, Brown-Frandsen K, et al. Liraglutide and Renal Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377:839.

Writing Committee for the Type 1 Diabetes TrialNet Oral Insulin Study Group, Krischer JP, Schatz DA, et al. Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes: A Randomized Clinical Trial. JAMA 2017; 318:1891.

Marcovecchio ML, Chiesa ST, Bond S, et al. ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes. N Engl J Med 2017; 377:1733.





Davies M, Pieber TR, Hartoft-Nielsen ML, et al. Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA 2017; 318:1460.


Marso, Steven P., et al. "Liraglutide and cardiovascular outcomes in type 2 diabetes." New England Journal of Medicine 375.4 (2016): 311-322.

Wanner, Christoph, et al. "Empagliflozin and progression of kidney disease in type 2 diabetes." New England Journal of Medicine 375.4 (2016): 323-334.


Wysham, Carol, et al. "Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 2 diabetes: the SWITCH 2 randomized clinical trial." Jama 318.1 (2017): 45-56.

Documents

Endocrinologist Roper Endocrinology health/health... · 2018-02-20 · glycated albumin or fructosamine level Bergenstal RM, Gal RL, Connor CG, et al. Racial Differences in the Relationship