CLINIC AL PR AC TICE GUIDELINE S

MANAGEMENT OF
TYPE 2 DIABETES MELLITUS
(6th Edition)

Quick Reference Guide

for Healthcare Professionals

Malaysia Endocrine Ministry of Health Academy of Medicine Diabetes Malaysia Family Medicine Specialists
& Metabolic Society Malaysia Malaysia Association of Malaysia
 This Quick Reference Guide provides KEY MESSAGES and
Summary of the main recommendations in the CPG for the
Management of Type 2 Diabetes Mellitus, 6th edition

KEY MESSAGES

Risk-based screening for pre- and/or T2DM in adults should be performed in

individuals >30 years of age and repeated annually, as ~50% of people with
diabetes are undiagnosed.

HbA1c ≥6.3% (IFCC ≥ 45 mmol/mol) performed by an NGSP-certified method,

standardised to DCCT assay is diagnostic of diabetes.

In asymptomatic individuals, 2 abnormal values (e.g. plasma glucose and HbA1c)

from the same blood sample is adequate for diagnosis of T2DM.

Pre-DM (IFG and/or IGT) predisposes these individuals to progression to overt

T2DM as well as increased CV risk. Lifestyle modification with weight loss is the
mainstay; but failing this, metformin can be initiated.

Remission of T2DM may be possible in some individuals with short duration

of disease, following significant and sustained weight loss by either caloric
restriction or bariatric surgery.

T2DM is a CVD defining disease, and patients should have their other CVD risk
factors, e.g. blood pressure, lipids treated aggressively and closely monitored.

Target HbA1c is individualised; ≤6.5% for those young, uncomplicated, with short
duration of disease; while <7.0% would be appropriate for most other adult
T2DM individuals.

Achieving HbA1c target early, from diagnosis and maintaining glucose control
for as long as possible, will result in persistent benefits and reduction of
complications in the long-term (Metabolic memory).

Metabolic associated fatty liver disease (MAFLD)* is a new proposed

nomenclature to replace NAFLD as it includes a key driver of this disease which,
is presence of metabolic dysfunction. NAFLD is increasingly recognised as a co-
morbidity associated with T2DM. If left unchecked, it can lead to liver cirrhosis
and hepatocellular carcinoma. NAFLD is also associated with higher CV risk and
aggressive management of CV risk, including statin therapy is indicated.

Recent CVOTs have proven that 2 classes of glucose-lowering agents (GLDs)

significantly reduce MACE outcomes, in people with established ASCVD or are at
high-CV risk, beyond their glucose-lowering effects; GLP1-RAs and SGLT2-i. The
data from these trials have resulted in paradigm shifts in recommendations for
choice of therapeutic agents.

SGLT2-i have also been proven to be reno-protective, delaying progression to

end-stage renal failure, >40% reduction in eGFR or renal death. This is the 2nd
class of therapy proven to be reno-protective, apart from RAS-blockers.

The newer therapeutic agents are expensive, and may not be affordable to
many. In these people, achieving HbA1c remains an important goal.

*NAFLD will be used in this edition of the T2DM CPG instead of MAFLD.
For expansion of abbreviations, refer to the main CPG document.
 Values for diagnosis*
(A) Diagnostic value for T2DM based on venous plasma glucose
Fasting Random
≥7.0 mmol/L ≥11.1 mmol/L

(B) Diagnostic values for pre-diabetes and T2DM based on HbA1c

Normal Pre-DM DM
<5.7 % 5.7- <6.3% ≥6.3%
(<39 mmol/mol) (39-44 mmol/mol) (≥45 mmol/mol)

(C) Diagnostic values for glucose intolerance and T2DM based on OGTT
Category 0 hr 2 hr
Normal <6.1 <7.8
IFG 6.1-6.9 -
IGT - 7.8 -11.0
DM ≥7.0 ≥11.1
* In asymptomatic patients, a repeat blood test on another day or 2 abnormal values (1 glucose + HbA1c in the same sample) is
required to confirm diagnosis.

Management of T2DM
• At diagnosis of T2DM the following should be performed:
› detailed history and physical examination, focusing on key issues which will
affect treatment decision
› baseline investigations to assess ASCVD risk factors and complications of
T2DM
• Management is based on the results of the above.
• Management involves lifestyle modification, medications and patient education
encouraging self-care and empowerment.

3-monthly OR
Test Initial visit Every follow-up visit At annual visit
Physical examination
Weight √ √ √
Waist circumference √ √ √
BMI √ √
BP √ √ √
Eye
Visual acuity √ √
Fundoscopy/Fundus camera √ √
Feet
Pulses/ABI √ √ √
Neuropathy √ √ √
Dental check-up √ √
ECG √ √
Laboratory investigations
Plasma glucose √ √ √
HbA1c √ √ √
Lipid profile √ √
Creatinine/BUSE + eGFR √ √
LFT (AST, ALT) √ √
Urine microscopy √ √
Urine albumin/microalbumin/
√ √
spot morning urinary ACR
√: conduct test conduct test if abnormal on initial visit or symptomatic no test is required
Note: refer to main CPG for important notations.
 T2DM: Targets for control
Parameters Levels
Fasting or pre-prandial 4.4 mmol/L-7.0 mmol/L
Post-prandial 4.4 mmol/L-8.5 mmol/L
Glycaemic control
<7.0% (for most)
HbA1c
≤6.5 %***
Triglycerides ≤1.7 mmol/L
Male: >1.0 mmol/L
Lipids HDL-C
Female: >1.2 mmol/L
LDL-C+ ≤2.6 mmol/L
BP 130-139/70-79 mmHg
Exercise 150 minutes/week
Body weight If overweight or obese, aim for up to 10% weight loss in 6 months
***Young, healthy, short duration of T2D, no/minimal risk of hypoglycaemia, + Depending on risk category, i.e., moderate (<2.6
mmol/L), high (<1.8 mmol/L) and very high (<1.4 mmol/L).

Relationships between NGSP, IFCC HbA1c and estimated average glucose (eAG)
NGSP HbA1C (%) IFCC HbA1c (mmol/mol) eAG (mmol/L) (95% CI)
5.0 31 5.4 (4.2-6.7)
6.0 42 7.0 (5.5-8.5)
7.0 53 8.6 (6.8-10.3)
8.0 64 10.2 (8.1-12.1)
9.0 75 11.8 (9.4-13.9)
10.0 86 13.4 (10.7-15.7)
11.0 97 14.9 (12.0-17.5)
12.0 108 16.5 (13.3-19.3)

Individualised HbA1c targets based on patient profile

≤6.5 % (Tight) 6.6%-7.0% 7.1%-8.0% (Less tight)
• Newly and recently diagnosed • All others • Elderly patients
• Younger age • Presence of co-morbidities
• Healthier (no complications) • High risk of severe
• Low risk of hypoglycaemia hypoglycaemia; hypo
unawareness
• Short life expectancy

Principal recommendation: Medical nutrition therapy & lifestyle modification

• Weight loss of ≥7%-10% of initial body weight within 6 months has been proven to
be effective for diabetes prevention.
• Proper diet is crucial at all stages of management of diabetes including those on
medication.
• Meal plans that meet individualised caloric goals with a macronutrient distribution
that is consistent with healthful eating pattern is recommended for long-term
achievement of glycaemia, lipids and weight goals.
• Encourage foods with low GI in the Malaysian context because excessive rise in
post-prandial glycaemia is frequently observed.
• Encourage moderate-intensity exercise, at least 150 mins/week or at least 75 mins/
week of vigorous aerobic

Recommendations for SMBG

Mode of Breakfast Lunch Dinner
Treatment Pre Post Pre Post Pre Post / Pre-bed
Diet only √ √ - √ - √
OGLDs √ √ - √ - √
Insulin √ √ √ √ √ √
 Glucose-lowering agents (oral & injectable)
Drugs Formulation Minimum dose Maximum dose
Biguanides
Usual: 1000 mg BD
Metformin 500/1000 mg Initial dose: 500 mg OD
*Exception: 1000 mg TDS
Metformin SR 850 mg Usual dose: 850 mg BD 850 mg TDS
Initial dose: 500 mg OD
Metformin XR 500/750/1000 mg 2000 mg OD
Usual dose: 2000 mg OD
Sulphonylureas
Glibenclamide 5 mg 2.5 mg OD 10 mg BD
Gliclazide 80 mg 40 mg OM 160 mg BD
Gliclazide MR 60/30 mg 30 mg OM 120 mg OM
Glipizide 5 mg 2.5 mg OM 10 mg BD
Glimepiride 2/3 mg 1 mg OM 6 mg OM
Meglitinides
4 mg with main meals (not
Repaglinide 0.5/1/2 mg 0.5 mg with main meal
exceeding 16 mg daily)
α-glucosidase inhibitor
Initial dose: 50 mg OD
Acarbose 50/100 mg Usual dose: 50-100 mg take 100 mg TDS
at 1st bite of main meals
Thiazolidinedione
Rosiglitazone 4/8 mg 4 mg OD 8 mg OD
Pioglitazone 15/30 mg 15 mg OD 45 mg OD
DPP4-inhibitors
Sitagliptin 25/50/100 mg 25 mg OD 100 mg OD
Vildagliptin 50 mg 50 mg OD 50 mg BD
Saxagliptin 2.5/5 mg 2.5 mg OD 5 mg OD
Linagliptin 5 mg 5 mg OD 5 mg OD
SGLT2-inhibitors
Dapagliflozin 5/10 mg 5 mg OD 10 mg OD
Canagliflozin 100/300 mg 100 mg OD 300 mg OD
Empagliflozin 10/25 mg 10 mg OD 25 mg OD
Luseogliflozin 2.5/5 mg 2.5 mg OD 5 mg OD
Ertugliflozin 5/15 mg 5 mg OD 15 mg OD
GLP1-RA
Exenatide IR 5 μg/20 μL; 10 μg/40 μL 5 μg BD 10 μg BD
Exenatide ER 2 mg 2 mg weekly 2 mg weekly
Dulaglutide 0.75 mg/1.5 mg 0.75 mg weekly 1.5 mg weekly
Liraglutide 6 mg/mL 0.6 mg OD 1.8 mg OD
Lixisenatide 50 μg/mL; 100 μg/mL 10 μg OD 20 μg OD
Semaglutide 0.25/0.5 mg 0.25 weekly 1.0 mg weekly
Note: Dose escalations will depend on tolerability and according to the PI.

Efficacy of various GLDs

MET SU GLN AGI TZD DPP4-i SGLT2-i GLP1-RA Insulin
HbA1c  % 1.0-1.5 0.4-1.6 1.0-1.2 0.5-0.8 0.5-1.4 0.5-0.8 0.2-0.8 0.5-1.4 >1.5
FPG vs. PPG FPG Both PPG PPG FPG Both Both Both Both
Hypoglycaemia         
Weight change       –  
GI symptoms         
CHF         
CVD         
Bone loss         
Fluid Dose
DKD Avoid* Hypo Hypo  a † Hypo
ret’n adjustment
* Avoid if eGFR < 30ml/min/1.73m2; †avoid if eGFR < 15 ml/min/1.73m2; aSGLT2-i can be used until dialysis is initiated and has
proven reno-protection although glucose-lowering efficacy is reduced.
Increased risk Mild-mod risk Neutral Possible benefit Beneficial
Note: refer to main CPG for important notations
 Treatment algorithm: Newly diagnosed T2DM
Diagnosis of T2DM

Lifestyle modificationa

HbA1c <6.5% AND HbA1c 6.5-7.4% HbA1c 7.5-8.4% HbA1c 8.5-10.0% HbA1c >10.0% OR
FPG <6.0 mmol/L OR OR OR FPG >13.0 mmol/
FPG 6.0-7.9 FPG 8.0-9.9 FPG 10.0-13.0 Lƒ
Consider
mmol/L mmol/L mmol/L
metformin Basal/premixed
monotherapyb Mono- or dual- Dual combination Triple insulin therapy
therapyc with therapye with any combination +
If post prandial
combination of: therapye with any Combination
is >11.0 mmol/L Metformind OR
combination of: therapy
and/or metformin Metformin
SU OR
is not tolerated, Metformin
SU
consider one of DPP4-i Intensive insulin
SU
the following: Meglitinide therapy
GLP1-RA
Meglitinide +
Meglitinide AGI
SGLT2-i OGLD
AGI
AGI TZD
• Optimise dose
TZD Efficacious, low risk
DPP4-i of GLD agent in DPP4-i of hypoglycaemia and
subsequent 3-6 DPP4-i weight neutral
• Follow-up with GLP1-RA
months. Efficacious, risk of
HbA1c after 3-6 GLP1-RA
• Follow-up with SGLT2-i hypoglycaemia and
months weight gain
HbA1c after 3-6 SGLT2-i
• If HbA1c ≤6.5%, months Insulin
Efficacious, low risk
continue Insulin of hypoglycaemia and
• If HbA1c ≤6.5%, • Optimise dose
weight loss
with lifestyle of GLD agent in • Optimise dose
continue
modification. subsequent 3-6 of GLD agent in Moderate efficacy,
therapy low risk of
• If HbA1c >6.5%c months. subsequent 3-6 hypoglycaemia and
• Follow-up with months. weight neutral
HbA1c after 3-6 • Follow-up with
Moderate efficacy,
months HbA1c after 3-6 low risk of
months hypoglycaemia and
• If HbA1c ≤6.5%, weight gain
continue • If HbA1c ≤6.5%,
therapy continue Moderate efficacy,
low risk of
therapy hypoglycaemia and
weight loss

Modest efficacy, low

c. Consider addition of DPP4-i (delays loss of glycaemic control) when initiated early. risk of hypoglycaemia
Note: refer to main CPG for other important notations. and weight neutral

Treatment recommendations: Clinic follow-up

3-6 months after initiation of therapy

HbA1c above individualised target with

Lifestyle lifestyle modification + existing therapy
modification must
be maintained at
0.5%-1% above target 1%-2% above target >2% above target
every juncture of
T2DM treatment.
It should include Add 1 additional GLD Consider 2 GLDs from
Initiation of insulin±
strategies to lose from different class different classes*
GLP1-RA∫
weight, correct diet OR OR
OR
and incorporate Intensification of Intensification of
Intensification of
physical activities.f insulin (if already on insulin (if already on
insulin∫
insulin)∫ insulin)∫

Reassess HbA1c after 3-6 months**

Note: refer to main CPG for important notations
 Initiation and optimisation of insulin therapy
Newly diagnosed T2DM
• Symptomatic hyperglycaemia regardless of • T2DM on maximal OGLDs with HbA1c >7% or, >
HbA1c or FPG individualised target
• HbA1c >10% or FPG >13.0 mmol/L

Pattern of hyperglycaemia FPG + PPG

Not adequately controlled on maximum OGLD ± GLP1-RA

• Add basal insulin 10 U OD OR 0.1-0.2 U/kg/day • Premixed insulin OD/co-formulation OD at

• TITRATE based on FPG main meal
• Choose evidence based titration algorithm
• If hypoglycaemia, reduce dose by 10-20%

If HbA1c above target despite If FPG at target but glucose high • Co-formulation BD
adequate titration OR basal dose during the day, consider basal • TITRATE based on individual
>0.5 U/kg OR FPG at target insulin analogue need

Basal plus: • Premixed insulin BD

• Add prandial insulin 4 U/meal OR 10% • TITRATE based on
of basal dose individual need
• TITRATE prandial insulin by increasing
1-2 U OR 10-15% every 3 days
• If hypoglycaemia, reduce prandial
insulin by 10-20% • Premixed analogue insulin TDS
• Stepwise addition of prandial insulin

• Basal bolus regimen

Suggested treatment approach for specific patient profiles

LIFESTYLE MODIFICATION + METFORMIN
(unless intolerant or contraindicated / ½ dose at DKD stage 3B, stop at DKD stages 4-5)

If HbA1c not to individualised target

Note: Reaching HbA1c is the priority (Targets individualised). Cost of newer medications may render them inaccessible.
Use therapies that have been shown to be efficacious and safe.

Overweight / Increased risk

Normal weight DKD Stage 3-5α High risk CVD ASCVD Heart failure
obese of hypoglycaemia

Weight loss DPP4-i OR SGLT2-i SGLT2-i /

DPP4-i GLP1-RAx SGLT2-i
through lifestyle SU* (stop when GLP1-RA
modification^ initiating dialysis)
SU* GLP1-RA (if SGLT2-i
SGLT2-i GLP1-RA∫ SGLT2-i GLP1-RA
GLP1-RA/SGLT2-i (if DPP4-i given) given or vice-versa)
(contraindicated
at eGFR <15 ml/
GLP1-RA min/1.73m2) DPP4-iƒ DPP4-iƒ DPP4-iƒ
SGLT2-i TZD (if not on GLP1-RA)
(if SGLT2-i given or (if not on GLP1-RA) (if not on GLP1-RA)
vice-versa) OR SU OR SU* OR SU*
DPP4-i
DPP4-i GLP1-RA∫ GLP1-RA∫ SU* SU* SU*
(if not on GLP1-RA) (if DPP4-i given) (if DPP4-i given) (if DPP4- given)
SU*
Low dose SU (not advisable in
SU* Basal OR premixed (2nd generation) Stages 4-5) TZD TZD
Basal OR premixed
insulin (escalate to
insulin (escalate to
basal bolus/switch
basal bolus/switch
Basal OR premixed to analogues)+ Basal OR premixed Basal OR premixed Basal OR premixed
Basal OR premixed to analogues)+
insulin (escalate to insulin (escalate to insulin (escalate to insulin (escalate to
OR basal/bolus
basal bolus/switch basal bolus/switch basal bolus/switch basal bolus/switch
insulin analogues
to analogues)+ to analogues)+ to analogues)+ to analogues)+
Note: refer to main CPG for important notations.
 Dosage of GLDs in renal failure
Dose adjustment in renal failure
Mild (CKD 2) Moderate (CKD 3) Severe (CKD 4 & 5)
Generic Name Usual dose* (GFR 60-89) (GFR 30-59) (GFR <30)
Biguanide§
45-60: No dose
Metformin 500-1000 mg BD Continue adjustment Avoid
<45: 50% dose reduction
Sulphonylurea^
Glibenclamide 5 mg OD-10 mg BD Use with caution Avoid
Gliclazide 80 mg OD-160 mg BD No dose adjustment Caution
Gliclazide MR 30-120 mg OD No dose adjustment Caution
≥15: <15:
Glimepiride 1-6 mg OD Initiate with 1 mg OD
Caution Avoid
Glipizide 2.5 mg OD-10 mg BD No dose adjustment Caution
Meglitinides
Initiate at 0.5 mg with
Repaglinide 0.5-4 mg TDS No dose adjustment
meals
Alpha-glucosidase Inhibitor
≥25: <25:
Acarbose 25-100 mg TDS 50-100%
50-100% Avoid
Thiazolidinediones
Pioglitazone 15-45 mg OD No dose adjustment (caution with fluid retention risk)
DPP4-i
≥50: No dose
Sitagliptin 100 mg OD No dose adjustment adjustment 25 mg OD
30-<50: 50 mg OD
≥50: No dose adjustment
Vildagliptin 50 mg OD-BD No dose adjustment
<50: 50 mg OD (limited data)
>50: No dose adjustment
Saxagliptin 2.5-5 mg OD No dose adjustment
≤50: 2.5 mg OD
Linagliptin 2.5-5 mg OD No dose adjustment
GLP1-RAs
>50: No dose
adjustment
5 μg/20 μL;
Exenatide IR No dose adjustment 30-50: Caution in Avoid
10 μg/40 μL
initiating or escalating
dose from 5 to 10 mcg
>50: No dose
Exenatide ER 2 mg weekly No dose adjustment adjustment Avoid
30-50: Use with caution
≥15: No dose <15:
6 mg/mL No dose adjustment No dose adjustment
Liraglutide adjustment Avoid
3 mg No dose adjustment No dose adjustment Avoid
Lixisenatide 50 μg/mL; 100 μg/mL No dose adjustment No dose adjustment Avoid
≥15: No dose <15:
Dulaglutide 0.75-1.5 mg weekly No dose adjustment No dose adjustment
adjustment Avoid
0.5-1.0 mg ≥15: No dose <15:
Semaglutide No dose adjustment No dose adjustment
weekly adjustment Avoid
SGLT2 Inhibitors¶
45-60: No dose
Dapagliflozin 5-10 mg OD No dose adjustment adjustment Avoid
<45: Not recommended
45-60: 100 mg OD
Canagliflozin 100-300 mg OD No dose adjustment Avoid
<45: Not recommended
Empagliflozin 10-25 mg OD No dose adjustment No dose adjustment Avoid
45-60: No initiation
Ertugliflozin 5-15 mg OD No dose adjustment Avoid
< 45: Not recommended
Luseogliflozin 2.5-5 mg OD No dose adjustment <60: Not recommended Avoid
Insulin
Doses should be adjusted based on frequent monitoring to balance goals of glycaemic control with avoiding
hypoglycaemia. Long-acting tends to accumulate longer than short-acting insulin.
Dose escalation will depend on tolerability and according to the PI.
Note: refer to main CPG for important notations.