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MANAGEMENT OF HYPERTENTION

AND DIABETES MELITUS


OLEH DR AGUS LASTYA
SPPD
Overview :

SESI 1: TATALAKSANA HIPERTENSI


SESI 2: TATALAKSANA DIABETES MELITUS
TIPE 2
SESI 1: HIPERTENSI
PERMASALAHAN 4

Pada populasi usia 55 dengan tekanan darah yang


normal berisiko 90 persen menderita hipertensi.
Dimulai pada TD 115/75 risiko CVD meningkat
2x pada setiap peningkatan TDS/TDD 20/10mmHg
Pada 30% populasi dewasa tidak mengetahui
dirinya hipertensi.
Penderita Hipertensi berisiko 2,5 kali menjadi
diabetes dalam kurun waktu 5 tahun.
APA ITU HIPERTENSI

Suatu keadaan dimana upaya penurunan


tekanan darah akan memberikan manfaat
lebih besar dibandingkan dengan tidak
melakukannya(INA-SH 2014)
Hipertensi ditegakkan bila ditemukan TDS
>140 mmHg atau TDD >90 mmHg
Hypertension is defined as systolic blood
pressure (SBP) of 140 mmHg or greater,
diastolic blood pressure (DBP) of 90 mmHg
or greater, or taking antihypertensive
medication.
VI JNC, 1997
Blood Pressure
Classification
BP SBP DBP
Classification mmHg mmHg
Normal <120 and <80

Pre hypertension 120139 or 8089

Stage 1 140159 or 9099


Hypertension
Stage 2 >160 or >100
Hypertension
ETIOLOGI & F. RISIKO
Tipe Etiologi Hipertensi

Essential hypertension
95%
No underlying cause
Secondary hypertension
Renal
Parenchyma
Vascular
Endocrine
Misc.
2nd Hypertension

Secondary HTN
A. Renal (80%) AGN Renal Artery stenosis
CGN,
CPN,
Polycyst. K.D

B. Endocrine Adrenal Primary aldosteronism


Cushings syndrome
Pheochromocytoma
Acromegaly

Exogenous hormone Oral contraceptive


Glucocorticoids
C. Misc. Coarctation of the aorta
Pregnancy Induced HTN
Sleep Apnea Syndrome.
Faktor Predisposisi:8

Usia Lanjut
Sex (Pria dan Wanita pasca menopause)
Riwayat Keluarga dengan penyakit
kardiovaskular
Sedentary life style & psycho-social
stress
Smoking ,High cholesterol diet, Low fruit
consumption
Obesity
Diabetes dan Dislipidemia
Konsumsi Alkohol
NEXT STEP..
Hypertension
Heart Left
Gangrene of the
Failure Ventricular Myocardial
Lower Hypertrophy Infarction
Extremities
Aortic Coronary
Aneurym Heart Disease
HYPERTENSION
Hypertensive
Blindness encephalopath
Cerebral y
Chronic
Stroke Preeclampsi Hemorrhag
Kidney
a/Eclampsia e
Failure
Haemodynamic Pattern in
Hypertension
Haemodynamic Pattern in
Hypertension

Young : BP = CO X PR

Elderly : BP = CO X PR
Pengukuran Tekanan Darah

Pengukuran di Klinik
Pada kesempatan pertama ukur kedua
lengan.
Pada populasi lansia ukur minimal 2 posisi.
Pengukuran Mandiri
Pada populasi White Coat hypertension
Pada populasi Masked hypertension
Risiko hipotensi karena obat
Hipertensi Sekunder-TOD
Pemeriksaan Penunjang
Managing
Hypertension

Goals of therapy
Lifestyle modification
Pharmacologic treatment
Algorithm for treatment of hypertension
Follow up and monitoring
Target Th/..

Reduce Cardiac and renal morbidity and mortality.

Treat to BP <140/90 mmHg in patients with/o


diabetes or chronic kidney disease.

BP < 150/90 in special population elderly (JNC 8)


Tatalaksana Hipertensi

Konsep Pencegahan:
Primer : Pola Hidup, IMT, DASH, 1
sendok the garam dapur , aerobik 30
mnt 4 x/mgg, dan tidak merokok.
Sekunder : cek tekanan darah rutin ,
pengobatan tepat.
Tersier : cegah komplikasi dan
peningkatan kualitas hidup.
Classification and
management of blood
pressure for adults
Hipertensi Tidak Terkendali

Hipertensi resisten
Terjadi peningkatan TD akut pada pasien
kronis
Hipertensi pada usia kurang dari 30 tahun
tanpa risiko.
Hipertensi terakselerasi.
Resistant
Hypertension :
Improper blood pressure measurement
Volume overload
Excess sodium intake
Volume retention from kidney disease
Nonadherence
Inadequate doses & Inappropriate combinations
Nonsteroidal anti-inflammatory drugs; cyclooxygenase 2
inhibitors
Sympathomimetics (decongestants, anorectics)
Steroids
Excess alcohol intake
SESI 2:
Tatalaksana
Diabetes
(T2DM)
DR AGUS LASTYA EKA P SPPD
KLASIFIKASI DAN DIAGNOSIS

1. Type 1 diabetes
2. Type 2 diabetes
3. Gestational diabetes mellitus (GDM)
4. Specific types of diabetes due to other
causes.
DIAGNOSTIC TESTS FOR
DIABETES
A1C >6.5%. The test should be performed in a laboratory using a
method that is certied and standardized
OR
FPG >126 mg/dL (7.0 mmol/L). Fasting is dened as no
caloric intake for at least 8 h.*
OR
2-h PG > 200 mg/dL (11.1 mmol/L) during an OGTT. The test
should be performed as described by the WHO, using a glucose
load containing the equivalent of 75 g anhydrous glucose
dissolved in water.*
OR
In a patient with classic symptoms of hyperglycemia or
hyperglycemic crisis, a random plasma glucose > 200 mg/Dl
(11.1 mmol/L).
Screening Test
T2DM
CATEGORIES OF INCREASED
RISK FOR DIABETES

Testing to assess risk for future diabetes in


asymptomatic people should be considered in
adults of any age who are overweight or obese
(BMI >25 kg/m2 or >23kg/m2 in Asian
Americans) and who have one or more
additional risk factors for diabetes.
For all patients, particularly those who are
overweight or obese, testing should begin at age
45 years.
Categories of prediabetes

FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL 6.9


mmol/L) (IFG)
OR
2-h PG in the 75-g OGTT 140 mg/dL (7.8 mmol/L)
to 199 mg/dL(11.0 mmol/L) (IGT)
OR
A1C 5.76.4%
Initial Evaluation
In Diabetes
Ax.
Prevention or
Delay of Type 2
Diabetes
Patients with:
impaired glucose tolerance (IGT) A,
impaired fasting glucose (IFG) E, or an
A1C 5.76.4% E
should be counseling for targeting loss of 7% of body weight and
increasing moderate-intensity physical activity (such as brisk walking) to
at least 150 min/week.

Metformin therapy for prevention of type 2 diabetes may be


considered in those with
IGT A,
IFG E, or an
A1C 5.76.4% E,
especially for those with BMI .35 kg/m2, aged ,60 years, and women
with prior gestational diabetes mellitus (GDM). A
Glycemic Targets
Why Hb A1C..

Lowering A1C to approximately 7% or less has been


shown to reduce microvascular complications of diabetes, and,
if implemented soon after the diagnosis of diabetes, it is
associated with long-term reduction in macrovascular disease.
Therefore, a reasonable A1C goal for many nonpregnant
adults is 7%. B
Preprandial capillary plasma glucose 80130 mg/dL (4.4
7.2 mmol/L)
Peak postprandial capillary plasma glucose ,180 mg/dL
(,10.0 mmol/L)
A1C(%) in Daily Practice
Approaches to
Glycemic
Treatment
Multiple, Complex
Pathophysiological
Abnormalities in T2DM
pancreatic
incretin insulin
effect secretion
pancreatic
_ glucagon
secretion
gut ?
carbohydrate
delivery & HYPERGLYCEMIA
absorption

+ peripheral
hepatic renal glucose
glucose glucose uptake
production excretion
Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011
Multiple, Complex
Pathophysiological
Abnormalities in T2DM
GLP-1R Insulin
agonists pancreatic
incretin Glinides S U s insulin
effect secretion
DPP-4 pancreatic
inhibitors glucagon
_ secretion
gut ?
carbohydrate
delivery & HYPERGLYCEMIA
absorption
Metformin TZDs
_

+ SGL2 i
peripheral
hepatic renal glucose
glucose glucose uptake
production excretion
Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011
Oral Mechanism Advantages Disadvantage Cos
Class s t
Biguanide Activates AMP- Extensive Gastrointestinal Low
s kinase (?other) experience Lactic acidosis
Hepatic No hypoglycemia (rare)
glucose Weight neutral B-12 deficiency
production ? CVD
Contraindications
Sulfonylu Closes KATP Extensive Hypoglycemia Low
reas experience Weight
channels
Microvascular Low durability
Insulin
risk ? Blunts
secretion
ischemic
preconditioning
Meglitinid Closes K Postprandial Hypoglycemia Mod
ATP
es glucose Weight .
channels
Dosing flexibility ? Blunts
Insulin
ischemic
secretion
preconditioning
Dosing
frequency

Diabetes Care 2015;38:140-149;


TZDs 1. Properties
Table of anti-hyperglycemic
PPAR- activator Weight
No hypoglycemia agents Low
Diabetologia2015;58:429-442
Oral Mechanism Advantages Disadvantag Cost
Class es
- Inhibits - No hypoglycemia Mod
Glucosida glucosidase Nonsystemic Gastrointestina .
se Slows Postprandial l
inhibitors carbohydrate glucose Dosing
digestion / ? CVD events frequency
absorption Modest A1c
DPP-4 Inhibits DPP-4 No hypoglycemia Angioedema / High
inhibitors Increases incretin Well tolerated urticaria
(GLP-1, GIP) levels ? Pancreatitis
? Heart
failure

SGLT2 Inhibits SGLT2 in Weight GU infections High


inhibitors proximal nephron No hypoglycemia Polyuria
Increases BP Volume
glucosuria Effective at all depletion
stages LDL-C
Cr
(transient)
Diabetes Care 2015;38:140-149;
Table 1. Properties of anti-hyperglycemic agents Diabetologia2015;58:429-442
Injecta Mechanism Advantages Disadvantages Cost
ble
Class

GLP-1 Activates GLP-1 Weight Gastrointestinal High


recept R No hypoglycemia ? Pancreatitis
or Insulin, Postprandial Heart rate
agonist glucagon glucose Medullary ca
s gastric Some CV risk (rodents)
emptying factors Injectable
satiety Training
requirements
Insulin Activates insulin Universally Hypoglycemia Varia
receptor effective Weight gain ble
Myriad Unlimited efficacy ? Mitogenicity
Microvascular Injectable
risk Patient reluctance
Training
requirements

Diabetes Care 2015;38:140-149;


Table 1. Properties of anti-hyperglycemic agents Diabetologia2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education
Mono-
therapy Metformin
Efcacy* high
Hypo risk low risk
Weight neutral/loss
Side effects GI / lactic acidosis
Costs low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin Metformin Metformin Metformin Metformin Metformin


+ + + + + +
Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal)
therapy dione inhibitor inhibitor agonist
Efcacy* high high intermediate intermediate high highest
Hypo risk moderate risk low risk low risk low risk low risk high risk
Weight gain gain neutral loss loss gain
Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia
Costs low low high high high variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD

or DPP-4-i or DPP-4-i or TZD or TZD or TZD or DPP-4-i

or SGLT2-i or SGLT2-i or SGLT2-i or DPP-4-i or Insulin or SGLT2-i

or GLP-1-RA or GLP-1-RA or Insulin or Insulin or GLP-1-RA


or Insulin or Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
+
Combination
Figure 2. Anti-hyperglycemic
injectable Basal Insulin + Mealtime Insulin or GLP-1-RA
therapy
therapy

in T2DM: General DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education
Mono-
therapy Metformin
Efcacy* high
Hypo risk low risk
Weight neutral/loss
Side effects GI / lactic acidosis
Costs low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin Metformin Metformin Metformin Metformin Metformin


+ + + + + +
Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal)
therapy dione inhibitor inhibitor agonist
Efcacy* high high intermediate intermediate high highest
Hypo risk moderate risk low risk low risk low risk low risk high risk
Weight gain gain neutral loss loss gain
Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia
Costs low low high high high variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD

or DPP-4-i or DPP-4-i or TZD or TZD or TZD or DPP-4-i

or SGLT2-i or SGLT2-i or SGLT2-i or DPP-4-i or Insulin or SGLT2-i

or GLP-1-RA or GLP-1-RA or Insulin or Insulin or GLP-1-RA


or Insulin or Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
+
Combination
Figure 2. Anti-hyperglycemic
injectable Basal Insulin + Mealtime Insulin or GLP-1-RA
therapy
therapy

in T2DM: General DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education
Mono-
therapy Metformin
Efcacy* high
Hypo risk low risk
Weight neutral/loss
Side effects GI / lactic acidosis
Costs low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin Metformin Metformin Metformin Metformin Metformin


+ + + + + +
Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal)
therapy dione inhibitor inhibitor agonist
Efcacy* high high intermediate intermediate high highest
Hypo risk moderate risk low risk low risk low risk low risk high risk
Weight gain gain neutral loss loss gain
Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia
Costs low low high high high variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD

or DPP-4-i or DPP-4-i or TZD or TZD or TZD or DPP-4-i

or SGLT2-i or SGLT2-i or SGLT2-i or DPP-4-i or Insulin or SGLT2-i

or GLP-1-RA or GLP-1-RA or Insulin or Insulin or GLP-1-RA


or Insulin or Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
+
Combination
Figure 2. Anti-hyperglycemic
injectable Basal Insulin + Mealtime Insulin or GLP-1-RA
therapy
therapy

in T2DM: General DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education
Mono-
therapy Metformin
Efcacy* high
Hypo risk low risk
Weight neutral/loss
Side effects GI / lactic acidosis
Costs low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin Metformin Metformin Metformin Metformin Metformin


+ + + + + +
Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal)
therapy dione inhibitor inhibitor agonist
Efcacy* high high intermediate intermediate high highest
Hypo risk moderate risk low risk low risk low risk low risk high risk
Weight gain gain neutral loss loss gain
Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia
Costs low low high high high variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD

or DPP-4-i or DPP-4-i or TZD or TZD or TZD or DPP-4-i

or SGLT2-i or SGLT2-i or SGLT2-i or DPP-4-i or Insulin or SGLT2-i

or GLP-1-RA or GLP-1-RA or Insulin or Insulin or GLP-1-RA


or Insulin or Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
+
Combination
injectable Basal Insulin + Mealtime Insulin or GLP-1-RA
therapy DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education
Mono-
therapy Metformin
Efcacy* high
Hypo risk low risk
Weight neutral/loss
Side effects GI / lactic acidosis
Costs low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin Metformin Metformin Metformin Metformin Metformin


+ + + + + +
Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal)
therapy dione inhibitor inhibitor agonist
Efcacy* high high intermediate intermediate high highest
Hypo risk moderate risk low risk low risk low risk low risk high risk
Weight gain gain neutral loss loss gain
Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia
Costs low low high high high variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD

or DPP-4-i or DPP-4-i or TZD or TZD or TZD or DPP-4-i

or SGLT2-i or SGLT2-i or SGLT2-i or DPP-4-i or Insulin or SGLT2-i

or GLP-1-RA or GLP-1-RA or Insulin or Insulin or GLP-1-RA


or Insulin or Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
Figure 2A. Anti- +
Combination
hyperglycemic
injectable therapy Basal Insulin + Mealtime Insulin or GLP-1-RA
therapy
in T2DM:

DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education
Mono-
therapy Metformin
Efcacy* high
Hypo risk low risk
Weight neutral/loss
Side effects GI / lactic acidosis
Costs low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin Metformin Metformin Metformin Metformin Metformin


+ + + + + +
Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal)
therapy dione inhibitor inhibitor agonist
Efcacy* high high intermediate intermediate high highest
Hypo risk moderate risk low risk low risk low risk low risk high risk
Weight gain gain neutral loss loss gain
Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia
Costs low low high high high variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD

or DPP-4-i or DPP-4-i or TZD or TZD or TZD or DPP-4-i

or SGLT2-i or SGLT2-i or SGLT2-i or DPP-4-i or Insulin or SGLT2-i

or GLP-1-RA or GLP-1-RA or Insulin or Insulin or GLP-1-RA


or Insulin or Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
Figure 2B. Anti- +
Combination
hyperglycemic
injectable therapy Basal Insulin + Mealtime Insulin or GLP-1-RA
therapy
in T2DM:

DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education
Mono-
therapy Metformin
Efcacy* high
Hypo risk low risk
Weight neutral/loss
Side effects GI / lactic acidosis
Costs low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin Metformin Metformin Metformin Metformin Metformin


+ + + + + +
Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal)
therapy dione inhibitor inhibitor agonist
Efcacy* high high intermediate intermediate high highest
Hypo risk moderate risk low risk low risk low risk low risk high risk
Weight gain gain neutral loss loss gain
Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia
Costs low low high high high variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD

or DPP-4-i or DPP-4-i or TZD or TZD or TZD or DPP-4-i

or SGLT2-i or SGLT2-i or SGLT2-i or DPP-4-i or Insulin or SGLT2-i

or GLP-1-RA or GLP-1-RA or Insulin or Insulin or GLP-1-RA


or Insulin or Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
Figure 2C. Anti- +
Combination
hyperglycemic
injectable Basal Insulin + Mealtime Insulin or GLP-1-RA
therapy
therapy

in T2DM: DiabetesCare2015;38:140149;Diabetologia 2015;58:429-442
Special population
Framework for considering treatment goals for
glycaemia, blood pressure, and dyslipidemia in
older adults with diabetes
Management of Diabetes in
Pregnancy

Potentially teratogenic medications ( ACE


inhibitors, statins ) should be avoided. B
Due to alterations in red blood cell turnover that
lower the normal A1C level in pregnancy, the
A1C target in pregnancy is ,6% if this can be
achieved without signicant hypoglycemia.
B
Medications widely used in pregnancy include
insulin, metformin, and glyburide; most oral
agents cross the placenta or lack long-term safety
data. B
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