Diabetes overview

Dr S Al-Falahi
Learning Objectives
Update on epidemiology and background
Targeting the patient: What’s new in glucose/A1c targets?
Choosing therapy for your patient with type 2 diabetes: When
to use which meds and when to avoid
Exploring unique patient factors that drive pharmacologic
choices in type 2 diabetes: New Focus on Cardiovascular and
Renal risk reduction
Innovations in insulin therapy and glucose monitoring: 2 steps
forward (increased safety and easier monitoring) and 1 step back
(cost/access)
Diabetes in the US: Who is bearing the brunt?

National Centre for Chronic Disease Prevention and Health Promotion Division of Diabetes Translation; based on NHIS data
T2D is progressive and requires changes to therapeutic
strategy over time
 Can we change this natural history?

▪️Gastric bypass resolved type 2 diabetes in

nearly 68.2% of patients (n=4,434) within 5
years of surgery.3
▪️Now recommended for BMI 30 or over in patients
with diabetes who fail medical weight loss.

1. Mingrone G, et al. N Engl J Med. 2012 Apr 26;366(17):1577-85.

2. Schauer PR, N Engl J Med. 2012 Apr 26;366(17):1567-76.
3. ArterburnDE,etal.ObesSurg.2013Jan;23(1):93-102.
Case: Part1: 72 year old woman with T2D for
25 years who suffered an MI 3 months ago

Successful revascularization with stent LAD. EF last week

65%
Complications: Nephropathy with GFR 48, mild macular
edema bilateral, mild neuropathy. Osteopenia. Obesity (BMI
32)
Regimen: MetforminER 1000mg daily, glipizide 10 BID. Statin,
ACE-inhibitor, antiplatelet therapy.
BP 148/94. A1c 8.2% GFR 52, BMI 32
Case: Part1: 72 year old woman with T2D for 25 years
who suffered an MI 3 months ago. A1c 8.2%

Which of the following approaches is best regarding her A1c target?

A. Given her age, A1c below 8.5% is reasonable

B. A1c should be lowered to under 8% to slow
progression of microvascular disease, but how far below
depends on other factors
C. A1c should be lowered to under 7% to prevent
progression of microvascular disease
D. A1c is not reliable over age 65 and she should check
glucose 4 times daily as a next step
Case: Part1: 72 year old woman with T2D for 25 years
who suffered an MI 3 months ago. A1c 8.2%

Which of the following approaches is best regarding her A1c target?

A. Given her age, A1c below 8.5% is reasonable

B. A1c should be lowered to under 8% to slow
progression of microvascular disease, but how far below
depends on other factors
C. A1c should be lowered to under 7% to prevent
progression of microvascular disease
D. A1c is not reliable over age 65 and she should check
glucose 4 times daily as a next step
Let’s start with Targets: How do we define
“glycemic control”?
 Summary of glycemic control trial results
Early glycemic control upon diagnosis of diabetes substantially
reduces risk of microvascular disease, in type 2 diabetes and
based on long term follow up of older trials, cardiovascular
events, stroke and death.
Pushing for lower targets (e.g., <7%) years after diagnosis yields
no cardiovascular benefits.
Lower targets in older patients with cardiovascular disease pose
higher risk in some patients.
-In Accord, deaths were in those in the intensive group who had a
higher average A1c during the trial and did not meet trial HbA1c goal
Riddle MC, et al. Diabetes Care. 2010
May;33(5):983-90. doi: 10.2337/dc09-1278. PubMed PMID:
20427682
Expert recommendations: ?Consensus

* Both statements have caveats allowing for more aggressive HbA1c goals based on patient
preference and overall health.
Davies MJ, et al. Diabetologia. 2018;61:2461-2498.
Garber AJ, et al. Endocrine Practice. 2018;24:91-120.
Diabetes Care. 2019;42(Supp 1).Qaseem A, et al. Ann
Intern Med. 2018; 168:569-76. AGS. J Am Geriatr Soc.
2013;61:2020-2026.
Does age matter? Consider Heterogeneity In The
Older Patient Population
Setting treatment goals will depend on the health status and social support
of each individual patient.
Assess each patient for:
– Cognitive ability
– Cardiovascular co-morbities
– Other medical conditions such as malignancy, hepatic
insufficiency
– Life expectancy
Assess each patient for social support:

– Family resources
– Community
resources
 Correlates of Dementia and Glucose
Higher A1C levels predict lower scores on
tests such as the “Clock in a Box”

– Recent study of 60 patients over age 70 found average A1C of

those with good scores to be 7.5% and those with poor scores to
be 8.7%
– But does poor glucose control cause dementia or is poor
control a result of cognitive decline?

Diabetes Care 29:1794–1799, 2006

What about Hypoglycemia and Cognition?
A 4 year study of 800 T2DM older patients found that one episode of
severe hypoglycemia tripled risk of dementia.
Again raising question: Does the dementia increase risk of hypoglycemia or
vice versa?
In the ACCORD trial, intensive treatment neither increased nor
diminished the risk of cognitive decline which progressed in both
groups. This may be related to unique characteristics of trial
participants.

Diabetes Care. 2019;42(1):142-147.

Diabetologia. 2017;60(1):69-80.
Detrimental effects of hypoglycemia

Falls
Seizures
Increase in CV mortality
Arrythmias
Causative or marker of vulnerability still debated

. Diabetes Care. 2019;42(1):157-163.

 New ENDO guideline: Overall health should determine
treatment targets in patients age 65 and over

* Does not include diabetesADL: Shared decision making: individualised targets may be
activities of daily living (e.g., eating, lower or higher
bathing, dressing)IADL: instrumental
activities of daily living (e.g., Adapted from: Leroith, et al. Managing Diabetes in the Older Adult. A Clinical Practice Guideline. JCEM in press.
managing money, doing housework) Cigolle, et al..J Gerontol A Biol Sci Med Sci 67 (12):1313-20, 2012; and Kirkman, et al. Diabetes Care. 2012.
Choosing therapies for Type 2 Diabetes
The New “Big Chart” for Diabetes Rx
Half-Century of HTN & T2DM Medications in U.S.
Glucose Lowering Drugs Classes
Still the first choice: Metformin
Metformin available since 1995.
Mechanism: reduce hepatic glucose output. May also increase
insulin sensitivity.
Dosing: slow titration, with meals, 2000 mg/day maximal
effective dose.
A1c lowering: 1-2%
Pros: weight loss, no hypoglycemia, efficacy, metabolic
improvements, outcome measurements, history of use. Possible
cancer prevention effec
Cons: GI side-effects, renal insufficiency and lactic acidosis.
Updated Metformin–CKDPrescribing
Guidelines (April 2016)
Obtain eGFR before starting metformin and annually
Obtain eGFR before starting metformin and annually
Contraindicated in patients with eGFR <30
More frequently in those at risk for renal impairment (e.g., elderly)
Avoid starting in patients with eGFR between 30-45.
If IfeGFR falls below 45:
eGFR falls below 45:
Contraindicated in patients with eGFR <30
Assess benefits and risks of treatment
Avoid
D/C starting
if eGFR in patients
falls below 30. with eGFR between 30-
45.

http://www.fda.gov/Drugs/DrugSafety/ucm493244.htm (ac
 Sulfonylureas
Available since 1954.
Names: Glipizide, Glimeperide,
Highest risk profile (do not use):
Glyburide
Mechanism: bind to SU receptor, stimulates insulin secretion = the
insulin squeeze
Dosing: prior to meals, glucose-lowering effect plateaus around 1⁄2
max dose.
A1c lowering: 1-2%
Pros: long history of use, cost, efficacy, daily dosing, outcomes
measurements.
Cons: weight gain, hypoglycemia, (CV effects, beta- cell decline?),
caution with renal and liver dysfunction.
TZDs are affordable and effective but should I
use them?
rosiglitazone pioglitazone
Meta-analysis1 of all Meta-analysis3 of 19 trials
available randomised trials
The primary outcome (death,
- MI risk increased 43% (p=0.03) non- fatal MI, non-fatal stroke)
- CV death risk increased 64% was 18% LESS common with
(p=0.06) pioglitazone (p=0.005)
- Risk of CV death was double -Other benefits4.4%
Pioglitazone: from RCTs:
the comparator (p=0.02) NASH,
MI risk confirmed with - Control: 5.7%
Stroke risk after TIA
longer- term meta-analysis2
Case:Part2: 72yearoldwomanwithT2Dfor25 years
who suffered an MI 3 months ago. A1c 8.2%

Successful revascularization with stent LAD. EF last week 65%

Complications: Nephropathy with GFR 48, mild macular
edema bilateral, mild neuropathy. Obesity (BMI 32)
Other conditions: Obstructive sleep apnea; Osteoporosis
Regimen: MetforminER 1000mg daily, glipizide 10 BID.
Statin, ACE-inhibitor, antiplatelet therapy.
BP 148/94. A1c 8.2% GFR 52. BMI 32
 Case:Part2: 72yearoldwomanwithT2Dfor25 years
who suffered an MI 3 months ago. A1c 8.2%
Which of the following is the best strategy for optimising her diabetes medication
regimen?

A. Continue metformin. Add GLP-1 receptor agonist and taper

glipizide to off
B. Continue metformin. Add SGLT2 inhibitor empagliflozin and
taper glipizide to off
C. Continue current regimen, add low dose long acting insulin
at bedtime (e.g. glargine).
D. Continue current regimen. Add pioglitazone 15mg daily
 Case:Part2: 72yearoldwomanwithT2Dfor25 years
who suffered an MI 3 months ago. A1c 8.2%
Which of the following is the best strategy for optimising her diabetes medication
regimen?

A. Continue metformin. Add GLP-1 receptor agonist and taper

glipizide to off
B. Continue metformin. Add SGLT2 inhibitor empagliflozin and
taper glipizide to off
C. Continue current regimen, add low dose long acting insulin
at bedtime (e.g. glargine).
D. Continue current regimen. Add pioglitazone 15mg daily
New Approach: Consider
“Perks” first

Diabetes Standards of Care

2019.
Efficacy: empagliflozin vs. placebo
• EMPA-REG OUTCOME: CV related death, non-fatal
MI and non-fatal stroke1

Reduced HF hospitalization or CV death by 34%2

HF rates: 5.7% for empagliflozin vs 8.5% for placebo
1. Zinman B, et al. N Engl J Med. 2015;373:2117-28.
2. Fitchett D, et al. Eur Heart J. 2016 Jan 26.
 Cardiovascular Outcome Trials

REWIND trial 2018

 Cardiovascular Outcome Trials

REWIND trial 2018

Preferred treatment options after lifestyle
and metformin are maximized

Utilise patient characteristics to select best agent when multiple options are available.
Review: When to AVOID a class
 Case:Part3:
78yearoldwomanwithT2Dfor31
years who suffered an MI 6 years
ago
6 years have passed. Overall well, EF normal
Current diabetes regimen:

A1c 7.2%-7.6%, more recently 9% with some overnight

glycosuria. In setting of UTI. Repeat A1c after UTI treatment is
9.2%. GFR has slowly declined over time, 52 to 40.
New mild cognitive impairment identified by you in this
setting as well.
Her daughter moved home for 1 week and assisted with
medications, reported her mother was taking them reliably
 Case:Part2: 78yearoldwomanwithT2Dfor 25
years who suffered an MI 6 years ago. A1c 9.2%

Which offollowing
Which of the the following is the
is the best strategy best strategy
for optimising her diabetesfor
medication regimen
now?
optimizing her diabetes medication regimen now?
A. Add nightly NPH or glargine. Stop metformin and
dulaglutide
B. Add SGLT2 inhibitor empagliflozin to current regimen.
C. Add Pioglitazone (Actos) 15mg to current regimen
D. Add nightly basal insulin, whichever she can afford.
Continue metformin and dulaglutide
 Case:Part2: 78yearoldwomanwithT2Dfor 25
years who suffered an MI 6 years ago. A1c 9.2%

Which offollowing
Which of the the following is the
is the best strategy best strategy
for optimising her diabetesfor
medication regimen
now?
optimizing her diabetes medication regimen now?
A. Add nightly NPH or glargine. Stop metformin and
dulaglutide
B. Add SGLT2 inhibitor empagliflozin to current regimen.
C. Add Pioglitazone (Actos) 15mg to current regimen
D. Add nightly basal insulin, whichever she can afford.
Continue metformin and dulaglutide
T2D is progressive and requires changes to therapeutic
strategy over time
 When should insulin be initiated?
Newly diagnosed patients

• Suspected or established type 1 diabetes

• Insulin deficiency symptoms
– Weight loss is most concerning for insulin deficiency in addition to dramatic “3 Ps”
• Very elevated plasma glucose concentrations – >300–350 mg/dL or HbA1c ≥10.0–12.0%

Diabetes Care. 2016;39:S52-

59.
When should insulin be
considered in T2D? Patient on
non-insulin therapy
Approach not changed for type 2 dm:
Adding basal insulin to noninsulin meds
can support insulin secretion/action
Initiating insulin

Based on ADA Standards of Care. 2019.

 Adverse Events from Insulin

Insulin is the second most common drug to cause ER visits in older

patients
95% of these visits are due to hypoglycemia
24% involved LOC or seizure
25% resulted in hospitalization
Rates up to 2.76 episodes/100 patient years have been reported
Who is at highest risk? The aging adult

Aging Dis. 2015;6(2):156-167.

 De-Intensify

JAMA Intern Med. 2015;175(3):356-362

Continuous glucose monitoring
 Integration of pump and CGM
T:slim with CGM

T:slim with CGM

MiniMed 670G Hybrid Closed loop system

Insulin Costs:
It’s not all about the sugars
(thank goodness)
Lipid Management and Aspirin
All T2DM patients regardless of age should be considered for
statin therapy unless concerns for polypharmacy in the very
older adult
– 9% reduction in mortality for every 1 mmol/l drop in LDL in large meta-
analysis with equal benefit in older age groups
Recent analysis of data on aspirin benefits for primary
prevention for CVD have shown offsetting increase risk of
bleeding in older patients so ASA is not recommended.
 Hypertension
Rates of hypertension in older T2DM can reach 60-80%

Trials showing benefit of intensive treatment

– ACCORD-BP testing systolic BP <140 vs <120 found

lower target decreased stroke risk
– ADVANCE compared 134/73 vs 140/75 (modest difference) yet showed 9%
improvement in micro and macrovascular outcomes with 14% reduction in
mortality and 18% reduction in renal outcomes with benefit in older subgroup
But...
Treating Hypertension
 Take Home Points
There are more therapeutic options than ever before for type 2
diabetes, allowing for more personalization (but also more
complexity)
Selecting treatment for the management of type 2 diabetes should
be done with specific goals in mind (which should be documented for
each patient)
Example Goals: Glucose target, weight loss, cardiovascular risk
reduction, minimizing side effects and/or polypharmacy, minimizing
cost, maximizing simplicity, minimizing hypoglycemia risk (ask: what
are my patient’s goals?)
Insulin therapy: approach the same, new tools appear to improve
the quality of life when patients can access them
 Selected references
American Diabetes Association. Standards of Medical Care in
Diabetes-2019 Abridged for Primary Care Providers. Clin
Diabetes. 2019 Jan;37(1):11-34. PMCID: PMC633611
Davies MJ, D'Alessio DA, Fradkin J,et al. Management of
Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report
by the American Diabetes Association (ADA) and the European
Association for the Study of Diabetes (EASD). Diabetes Care.
2018 Dec;41(12):2669-2701.PMCID: PMC6245208
Riddle M C et al. Diabetes Care 2010;33:983-990
Glycemic control targets:
Leroith, et al. Older adult guideline. JCEM, 2019
Davies MJ, et al. Diabetologia. 2018;61:2461-2498.
Garber AJ, et al. Endocrine Practice. 2018;24:91-
120. Diabetes Care. 2019;42(Supp 1).
Qaseem A, et al. Ann Intern Med. 2018; 168:569-76.
AGS. J Am Geriatr Soc. 2013;61:2020-2026