Strategi Tatalaksana DM

Terkini

UNTUNG SURAPATI

DEPARTEMEN PENYAKIT DALAM

RSSI
Pangkalan bun
2019
Type 2 DM is the most common form
of diabetes (DM). In this form, the body
does not produce enough insulin or the
cells ignore the insulin that is produced. ...
Insulin takes the sugar from the blood into
the cells.
Objectives
• 1. The epidemiology and pathophysiology of type 2
diabetes and how our understanding has evolved
• 2. Review diabetes treatment algorithms and updated
goals of therapy
• 3. Newer pharmacologic treatments for type 2 diabetes
and where they fit into our current strategy
Diabetes Epidemiology 1956-
2009
Estimated lifetime risk of developing diabetes for
individuals born in the United States in 2000

60
Total Non-Hispanic White
Non-Hispanic Black Hispanic
50

40
Percent

30

20

10

0
Men Women
As of 2017, an estimated 425 million people had diabetes worldwide with
type 2 diabetes making up about 90% of the cases.
This represents 8.8% of the adult population, with equal rates in both women
and men.

Trends suggest that rates will continue to rise.[9] Diabetes at least doubles a
person's risk of early death.

In 2017, diabetes resulted in approximately 3.2 to 5.0 million deaths.The

global economic cost of diabetes related health expenditure in 2017 was
estimated at US$727 billion. In the United States, diabetes cost
nearly US$245 billion in 2012.

Average medical expenditures among people with diabetes are about 2.3
times higher.
Diabetes as a progressive
disease
 Two basic underlying mechanisms lead to type 2
diabetes:
 Insulin resistance
 Impaired insulin secretion from beta cells within the
pancreas
Diabetes as a progressive
disease
 Up to 70-80% of beta cell function is lost at the time
of diagnosis of type 2 diabetes
 Generally, alterations in glucose handling have been
present for 5+ years prior to the laboratory diagnosis
of type 2 diabetes
 Newer therapies are being targeted at mechanisms of
preserving and improving beta cell function and
altering insulin resistance while reducing risk of
hypoglycemia
 β-Cell mass in Type 2 diabetes

3,5

3,0
-50%
b -Cell volume (%)

2,5

2,0 -63%
1,5

1,0

0,5

0,0
ND IFG T2DM ND T2DM
Obese Lean
Butler et al. Diabetes. 2003
ND=non-diabetic; IFG=impaired fasting glucose; T2DM=Type 2 diabetes mellitus
Recommendations and
Guidelines
Recommendations: A1C

 Perform the A1C test at least two times a year in

patients meeting treatment goals (and have stable
glycemic control) E

 Perform the A1C test quarterly in patients whose

therapy has changed or who are not meeting glycemic
goals E

 Use of point-of-care (POC) testing for A1C provides the

opportunity for more timely treatment changes E
Insulin Therapy in T2DM
 The progressive nature of T2DM should be regularly
& objectively explained to T2DM patients.

 Avoid using insulin as a threat, describing it as a

failure or punishment.

 Give patients a self-titration algorithm.

American Diabetes Association Standards of Medical Care in Diabetes.

Diabetes Care Volume 42, Supplement 1, January 2019
Correlation of A1C with
Average Glucose
Mean plasma glucose
A1C (%) mg/dL mmol/L
6 126 7.0
7 154 8.6
8 183 10.2
9 212 11.8
10 240 13.4
11 269 14.9
12 298 16.5
These estimates are based on ADAG data of ~2,700 glucose measurements over 3 months per A1C measurement in 507
adults with type 1, type 2, and no diabetes. The correlation between A1C and average glucose was 0.92. A calculator for
converting A1C results into estimated average glucose (eAG), in either mg/dL or mmol/L, is available at
http://professional.diabetes.org/eAG.
ADA. V. Diabetes Care. Diabetes Care 2014;37(suppl 1):S23; Table 8
 Recommendations:
Glycemic Goals in Adults
 A reasonable A1C goal for many non pregnant
adults is <7% (53 mmol/mol). A
 Consider more stringent goals (e.g. <6.5%) for
select patients if achievable without significant
hypos or other adverse effects. C
 Consider less stringent goals (e.g. <8%) for
patients with a history of severe hypoglycemia,
limited life expectancy, or other conditions that
make <7% difficult to attain. B
American Diabetes Association Standards of Medical Care in Diabetes. AMERICAN DIABETES ASSOCIATION STANDARDS OF MEDICAL CARE IN DIABETES.
Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56 DIABETES CARE VOLUME 42, SUPPLEMENT 1, JANUARY 2019
 Glycemic Recommendations for Non
pregnant Adults with Diabetes
Postprandial glucose may be targeted if A1C goals
are not met despite reaching preprandial glucose
goals.

American Diabetes Association Standards of Medical Care in Diabetes.

Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56 AMERICAN DIABETES ASSOCIATION STANDARDS OF MEDICAL CARE IN DIABETES.
DIABETES CARE VOLUME 42, SUPPLEMENT 1, JANUARY 2019
 Glycemic Recommendations for Nonpregnant Adults with Diabetes

A1C <7.0%*
(<53 mmol/mol)
Preprandial capillary 80–130 mg/dL*
plasma glucose (4.4–7.2 mmol/L)
Peak postprandial capillary plasma <180 mg/dL*
glucose† (<10.0 mmol/L)

* Goals should be individualized.

† Postprandial glucose measurements should be made 1–2 hours after the beginning of
the meal.

American Diabetes Association Standards of Medical Care in Diabetes.

Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56
Care Delivery Systems
33-49% of patients still do not meet targets for
A1C, blood pressure, or lipids.
14% meet targets for all A1C, BP, lipids, and
nonsmoking status.
Progress in CVD risk factor control is slowing.
Substantial system-level improvements are
needed.
Delivery system is fragmented, lacks clinical
information capabilities, duplicates services & is
poorly designed.
AMERICAN DIABETES ASSOCIATION STANDARDS OF MEDICAL CARE IN DIABETES.
PROMOTING HEALTH AND REDUCING DISPARITIES IN POPULATIONS. DIABETES CARE 2017; 40 (SUPPL. 1): S6-S10
Management of Hyperglycemia in Type 2
Diabetes: A Patient-Centered Approach
Position Statement of the American Diabetes Association (ADA) and
the European Association for the Study of Diabetes (EASD)
 American Diabetes Association Standards of Medical Care in Diabetes.
Diabetes Care Volume 42, Supplement 1, January 2019
Figure 6.1—Depicted are patient and disease factors used to determine optimal A1C targets. Characteristics and predicaments toward the left justify
more stringent efforts to lower A1C; those toward the right suggest less stringent efforts. A1C 7% = 53 mmol/mol.
 Impact of Intensive Therapy for Diabetes: Summary of Major Clinical Trials

Study Microvasc CVD Mortality

UKPDS      
DCCT /
EDIC*      

ACCORD   
ADVANCE   
VADT   
Initial Trial
Kendall DM, Bergenstal RM. © International Diabetes Center 2009

UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854. Long Term Follow-up
Holman RR et al. N Engl J Med. 2008;359:1577. DCCT Research Group. N Engl J Med 1993;329;977.
Nathan DM et al. N Engl J Med. 2005;353:2643. Gerstein HC et al. N Engl J Med. 2008;358:2545.
Patel A et al. N Engl J Med 2008;358:2560. Duckworth W et al. N Engl J Med 2009;360:129. (erratum: * in T1DM
Moritz T. N Engl J Med 2009;361:1024)
Pharmacologic Therapy
For Type 2 Diabetes
Recommendations: Pharmacologic Therapy For
T2DM
Metformin, if not contraindicated and if tolerated, is the
preferred initial pharmacologic agent for T2DM. A
Once initiated, metformin should be continued as long as
it is tolerated and not contraindicated; other agents,
including insulin, should be added to metformin. A
Consider insulin therapy (with or without additional
agents) in patients with newly dx’d T2DM who are markedly
symptomatic and/or have elevated blood glucose levels
(>300 mg/dL) or A1C (>10%). E

AMERICAN DIABETES ASSOCIATION STANDARDS OF MEDICAL CARE IN DIABETES.

DIABETES CARE VOLUME 42, SUPPLEMENT 1, JANUARY 2019
Newer Recommendations: Pharmacologic Therapy
For T2DM
Long-term use of metformin may be associated with
biochemical vitamin B12 deficiency, and periodic measurement
of vitamin B12 levels should be considered in metformin-treated
patients, especially in those with anemia or peripheral
neuropathy. B
For patients with type 2 diabetes who require an injectable
drug, a glucagon-like peptide 1 receptor agonist is preferred over
insulin. B
Among patients with type 2 diabetes who have established
atherosclerotic cardiovascular disease, SGLT2 inhibitors, or GLP-
1RAs with demonstrated cardiovascular disease benefit are
recommended as part of the antihyperglycemic regimen. A

American Diabetes Association Standards of Medical Care in Diabetes.

Diabetes Care Volume 42, Supplement 1, January 2019
Newer Recommendations: Pharmacologic Therapy
for T2DM

Among patients with atherosclerotic cardiovascular disease at

high risk of heart failure or in whom heart failure coexists, SGLT2i
are preferred. C
For patients with type 2 diabetes and chronic kidney disease,
consider the use of an SGLT2i or GLP1RA shown to reduce the
risk of CKD progression, CV events, or both. C

American Diabetes Association Standards of Medical Care in Diabetes.

Diabetes Care Volume 42, Supplement 1, January 2019
American Diabetes Association Standards of Medical Care in Diabetes.
Diabetes Care Volume 42, Supplement 1, January 2019
American Diabetes Association Standards of Medical Care in Diabetes.
Diabetes Care Volume 42, Supplement 1, January 2019
American Diabetes Association Standards of Medical Care in Diabetes.
Diabetes Care Volume 42, Supplement 1, January 2019
American Diabetes Association Standards of Medical Care in Diabetes.
Diabetes Care Volume 42, Supplement 1, January 2019
Newer Diabetes
Medications
 GLP-1: effects in humans
• Stimulates glucose-dependent
After food ingestion… insulin secretion

• Suppresses glucagon
secretion

• Slows gastric emptying

• Leads to a reduction of
GLP-1 is secreted from food intake
L-cells of the jejunum
and ileum • Improves insulin sensitivity

Long-term effects
That in turn… in animal models:

• Increase of β-cell mass

and improved β-cell function
 Incretin effect on insulin secretion
Control subjects (n=8) People with Type 2 diabetes (n=14)
80 80

60 60
Insulin (mU/l)

Insulin (mU/l)
40
Incretin 40
effect
20 20

0 0
0 60 120 180 0 60 120 180
Time (min) Time (min)

Oral glucose load

Intravenous glucose infusion
GLP-1 Receptor Agonists

Supraphysiologic doses of GLP-1

Increases glucose-dependent insulin secretion
Suppresses glucagon in fasting and postprandial states
Slows gastric emptying
Improves satiety
Robust A1c lowering power ~1-2%
Weight loss with minimal risk of hypoglycemia without
concomitant use of secretagogue or insulin
DPP-4 inhibitors

Decrease the rapid degradation of endogenous GLP-1 to allow it

to exert its effects longer
Generally targets post-prandial glucose values with a minimal
effect on fasting glucose
Generally a very tolerable drug class with minimal potential side
effects
Hypoglycemia rare without concurrent use of sulfonylureas or
insulin
Weight neutral
Sodium-glucose co-
transporter 2 inhibitors
Inhibits the SGLT2 co-transporter in the proximal tubule of
the nephron to increase glucose excretion
Excrete roughly 60-90g glucose per day in urine
Weight benefit by excreting calories
Minimal risk of hypoglycemia without concomitant use of
secretagogue or insulin
Does not require endogenous insulin secretion from the
pancreas, so can be used at any stage of disease
Fair A1c benefit (~1%)
SGLT-2i medications

Canagliflozin – 3 point MACE reduction

Dapagliflozin – Decreased heart failure admissions in
DECLARE
Empagliflozin – Decreased CV death
Ertugliflozin
 ADA-EASD Position Statement: Management of
Hyperglycemia in T2DM

KEY POINTS
• Glycemic targets & BG-lowering therapies must be individualized.

• Diet, exercise, & education: foundation of any T2DM therapy program

• Unless contraindicated, metformin = optimal 1st-line drug.
• After metformin, data are limited. Combination therapy with 1-2 other oral /
injectable agents is reasonable; minimize side effects.
• Ultimately, many patients will require insulin therapy alone / in combination with
other agents to maintain BG control.
• All treatment decisions should be made in conjunction with the patient (focus on
preferences, needs & values.)
• Comprehensive CV risk reduction - a major focus of therapy.
Thank you