IC 10 – Pharmacology of Diabetic Medications

Concept Explanations & Details

Metformin (Biguanide)
MoA : activate AMP-activated protein kinase
activated AMPK
a. increase no. of GLUT-4
b. reduce hepatic mitochondrial respiration
reduced ATP = ATP-dependent gluconeogensis x occur
c. inhibit hepatic glucagon signalling
interfere glucagon-induced signalling pathways

Indications - 1st line for diabetic control

- off-label use: PCOS for ovulation induction
- effects
a. reduce HbA1c by 1.5~2.0%
b. negligible weight gain and hypoglycaemia
c. possible reduction in CV events in T2DM pt

ADME Absorptio: PO F = 40~60% | DoA = 8~12 hrs

Distribution: rapidly distributed, minimal prot. binding, HL 3 hrs

Metabolism: N/A

Excretion: 90% excreted unchanged renally

x recommend for eGFR < 30 mL/min, reduce if eGFR < 45 mL/min

Dosing Immediate Release

: initiate at 500~850 mg OD, increase by 500~850 mg OD q1~2w
max. = 2500~2550 mg/d

Extended Release
: initiate at 500 mg OD, increases by 500 mg weekly
max. = 2000 mg OD

ADR : anorexia, GI disturbances, vit B12 deficiency (long-term), careful if

renal impairment or lactic acidosis

C/I - severe renal impairment (eGFR < 30 mL/min)

- hypoxic states or at risk for hypoxemia (high risk of lactic
acidosis)
HF, sepsis, respiratory failure, lilver impairment,
alcoholism, > 80 yo
avoid use in acute decompensated HF

Special Population : pregnancy may be considered for T2DM

DDI - ethanol increases risk for lactic acidosis

- iodinated contrast media (HL ~ 72 hrs)
: increases risk of AKI
temporarily withhold Metformin for ≥ 48 hrs after iodinated
contrast admin.
 Concept Explanations & Details

restart when renal function returns stable

- inhibitors / inducers of organic cationic transporters (OCT)
OCT inhibitors (e.g. Cimetidine, Dolutegravir, Ranolazine)
may increase Metformin conc. by reducing renal elimination

Glipizide (Sulphonylureas)
MoA : stimualte release of insulin from β-cells of pancreas islets
- main target: SU-receptor proteins on ATP-sensitive K+
channel
upon binding, K+ channel-mediated K+ efflux
- OD dosing improves adherence but more expensive

Indications - management of T2DM when hyperglycaemia cannot be

managed by diet & exercise alone
- can be used concomitantly with other glucose-lowering
agents and/or insulin
- 1st gen = Tolbutaminde / 2nd gen = Glipizide, Gliclazide,
Glibenclamide / 3rd gen = Glimepiride
- reduce HbA1c by 1.5%

ADME Absorption: PO F > 95% | onset = 0.5 hr | DoA = 12~24 hrs

Distribution: extensive protein binding | HL = 4 hrs

Metabolism: 90% hepatic metabolism

Excretion: 10% excreted unchanged in urine

Dosing - Tolbutamide: initial 1~2 g/d, maintenance 0.5~2 mg/d

- Gliclazide: 30~120 mg OD
- Glimepride: 1~4 mg OD (max. 8 mg/d)

ADR : hypoglycaemia (esp. in elderly), weight gain

C/I : hypersensitivity to any SUs

DDI - BB may mask S&Sx of hypoglycaemia

- disulfiram-like reactions with ethanol (1st >> 2nd / 3rd)
- CYP2C9 inhibitors (e.g. Amiodarone, 5-FU, Fluoxetine)
may increase con. of Glimepiride, Glipizide

Place in Therapy - take immediately before meal. Do NOT miss / delay any meal
- use with caution with irregular meal schedules (risk of hypo.)
- need to exercise to minimise weight gain S/E

–gliptins (DPP-4 Inhibitors)

MoA : bind to & inhibit DPP-4 enz. to reduce enzymatic degradation of
GLP-1
prolongs the action of endogenous incretins
stimulate β-cells fo increased glucose-stimulated insulin release
suppress α-cell-mediated glucagon release and hepatic glucose
 Concept Explanations & Details

production
decrease in blood glucose level

Indications - adjunct to diet and exercise in T2DM treatment. Used in

combi. with other anti-diabetic agents
- reduce HbA1c by 0.5~0.8% as monotherapy
x 1st-line often used as dual / triple combi.

ADME Absorption: PO F = 87%

Distribution: HL 10~12 hrs

Metabolism: low hepatic metabolism

Excretion: 80% excreted unchanged in urine

Dosing - Sitagliptin: 100 mg OD

- VLinagliptin: 5 mg OD
- Vildagliptin
- with Metformin / TZD: 50 mg BD
- with SU: 50 mg OD

Dosage Adjustments - Sitagliptin

- eGFR 30~45: 50 mg OD
- eGFR < 30: 25 mg OD
- Linagliptin
- N/A
- Vildagliptin
- CrCl > 50: 50 mg BD
- CrCl < 50: 50 mg OD

ADR : GI disturbances, flu-like Sx (headache, runny nose, sore throat), skin

reactions, hypersensitivity
use with caution in pt with Hx of pancreatitis

C/I hypersensitivity to any SUs

DDI - Sitagliptin: minimal increase in Digoxin conc.

- Linagliptin: CYP3A4 inducer may reduce Linagliptin conc.
- Vildagliptin: N/A

Place in Therapy - very mild in ADR

- low incidence of GI ADR, cheaper
- drawback: weight neutral, smaller HbA1c recution, no
“big 3” benefits (ASCVD, HF, CKD)

-gliflozins (SGLT2 inhibitors)

MoA : inhibit SGLT2 at nephron to decrease glucose reabsorption
decrease renal threshold for glucose
increase urinary glucose excretion
result = glucosuria, loss of calories, BP reduction
 Concept Explanations & Details

Indications - reduce HbA1c by 0.8~1.0%

- slight weight loss benefits
- other benefits: improvement in ASCVD, HF, CKD

ADME (Empa.) Absorption: PO F = 60~80%, Cmax 1~2 hrs

Distribution: HL 12 hrs (OD), highly protein bound (~90%)

Metabolism: minimal hepatic metabolism (glucuronidation)

Excretion: ~40% unchanged in faeces, ~27% unchanged in urine

Dosing - Empagliflozin: 10 mg OM w/ or w/o food

may increase to 25 mg OD
x initiate if eGFR < 45 mL/min
- Dapagliflozin: 5 mg OM w/ or w/o food
may increase to 10 mg OD if recution insufficient
x initiate if eGFR < 45 mL/min

Dosage Adjustment - eGFR >‰ 45 mL/min eG8R < 30

if alral on empar, uand ,

: x needed
0 Adose)
'
lo o)
.
can still womt ax mg
- eGFR < 45 mL/min
(
.

: discontinue

ADR - hypotension due to natriuresis, hypoglycaemia, renal

impairment, slightly increased LDL,urinary urgency
-∞ genital mycotic infection / UTI
- prevention: practise good genital hygiene
- increased risk of diabetic ketoacidosis
esp. euglycaemic DKA
-∞Fournier’s gangrene (inflammation of perineal region)

C/I : ESRD or dialysis

–glutides (GLP-1 Agonist)

MoA : activates GLP-1 receptor on pancreatic β-cells by activating
adenylate cyclase increased cAMP activated PKA trigger insulin
secretion & inhibit glucagon release

Indication - reduce appedite can result in weight loss

used in management of obese pt
- reduce risks of CV death, non-fatal MI and HF in T2DM pt
- recommended over insulin as 1st-line injectable when greater
glucose lowering is needed

ADME Absorption: SC OD dosing, F = 55%

Distribution: C16 FA binds to plasma proteins, HL 13 hrs

Metabolism: metabolised like polypeptides

Excretion: little or none excreted unchanged

 Concept Explanations & Details
wcighy managemest = snxenda
Dosing - Liraglutide aliabetes
a

3 = Victo ta

: SC OD, initial 0.6 mg 1.2 mg after 1w can increase up

to 1.8 mg lowdoses
s inipal provlcheglycacaanic ) x contro

- Dulaglutide to toral stanalve acc .

OMILY
for BM
…
getuseah ∞
: mimmosisef to az sse .

: SC once weekly, initial 0.75 mg 1.5 mg after 4w can

I semaglutidebrand fo
increase up to 3~4.5 mg
wesght manngemest
- Semaglutide (Ozempic)
Wegovy
=

: SC once weekly, initial 0.25 mg 0,5 mg after 4w can

.

increase up to 1 mg farthercountrol needed can ampto 2

s if
weelchy
, n
once
mag
- Semaglutide (Rybelsus)
.

: PO OD 30 mins before 1st meal, initial 3 mg 7 mg after

30d can increase up to 14 mg
0 .th doseh s
lowty CEtw3
ADR - common: N&V, diarrhoea, constipation, headache, tiredness
- severe: acute pancreatitis, acute cholecystiti, AKI
y S$ ; persisterntI IW , fewer

C/I - personal or family Hx of medullary thyroid carcinoma

- multiple endocrine neoplasia syndrome type 2 (MEN 2)
- Hx of pancreatitis

Place in Therapy : has cardiorenal benefits

–glitazones (Thiazolidinediones)
MoA : peroxisome proliferator-activated receptor-gamma (PPARgamma)
agonist to promote lucose uptake through GLUT-4

Indication : alternative to monoTx for pt who cannot take Metformin or in combi.

with other anti-diabetic agents
- reduce HbA1c by 0.5~1.4%
- beneficial in pt with fatty liver disease (NAFLD & NASH)

ADME - takes up to a month for maixmal effect

- hepatic elimination

Dosing : initial 14 or 30 mg OD can increase by 15 mg up to 45 mg OD

ADR - hepatotoxicity
x initiate / discontinue if ALT > x3 UNL
discontinue if S&Sx of hepatic dysfunction immediately
- fluid retention (caution in NYHA Class I or II HF)
monitor S&Sx of HF after initiation / dose adjustment
- fracture (increased risk esp. in women)
due to increase in bone resoprtion rate
- weight gain
- risk of bladder cancer
- increased risk of hypoglycaemia with insulin therapy

C/I - active liver disease

- symptomatic / Hx of HF (NYHA Class III, IV)
active or Hx of bladder cancer
IC 11 – Diabetes Mellitus (1)
Concept Explanations & Details

Classification of Diabetes ● Type 1

● Type 2
● Gestation DM
● Others
: infections, drugs, monogenic diabetes syndrome,
endocrinopathies, pancreatic destruction

T1DM Pathogenesis : absolute deficiency of pancreatic β-cell function due to

- immune mediated destruction
- +ve antibodies

Staging
Stages Characteristics

Stage 1 : autoimmunity (+ve Ab), normoglycaemia,

presymptomatic

Stage 2 : autoimmunity (+ve Ab), dysglycaemia,

presymptomatic

Stage 3 : autoimmunity (+ve Ab), new onset hyperglycaemia,

symptomatic

T2DM Pathogenesis : progressive loss of adequate β-cell insulin secretion on the

background of insulin resistance

Insulin resistance
: subnormal glucose response to endogenous/exogenous insulin
associated with
- obesity, lipodystrophy, stress, medications, pregnancy,
insulin Ab, genetic defects in insulin-signalling pathways

T1DM vs T2DM
Characteristics T1DM (5~10%) T2DM (90%)

Primary Cause autoimmune-mediated insulin resistance, impaired

pancreatic β-cell destruction, insulin secretion, -ve Ab
+ve Ab

Insulin Production (C-peptide absent normal / abnormal

level)

Age of Onset usually < 30 yo often > 40 yo, although

increasing prevalent in obese
children and younger adults

Onset of Clinical Presentation abrupt gradual

 Concept Explanations & Details

Physical Appearance often thin often overweight

Proneness to Ketosis frequent uncommon

Signs & Sx of DM Hyperclycaemia

: extreme thirst / frequent urination / dry skin / hunger / blurred vision
/ drowsiness / delayed healing

Hypoglycaemia
: shaking / tachycardia / sweating / dizziness / anxious / hunger /
impaired vision / weakness / headache / irritability

Common – 3 Ps
: Polydipsia (excessive thirst), Polyuria, Polyphagia (extreme hunger)

Parameters used to 1. fasting plasma glucose (FPG)

measure DM : after no calorie intake for ≥ 8 hrs
2. fandom or casual plasma glucose
: glucose level at any time of the day, regardless of meals
3. postprandial plasma glucose (PPG)
: usually 2 hrs after meal
can also be measured using a standardised 75 g oral
glucose tolerance test (OGTT)
4. haemoglobin A1c (HbA1c or A1c)
: average amt. of glucose over the past 3 months
HbA1c = 3 months average of {FPG + PPG}

Criteria for the Diagnosis of T2DM

HbA1c Interpretation Action Recommended
Diagnosis

High risk 6.0% and low probability no further test needed No diabetes
of DM below of diabetes unless symptomatic : maintain healthy
lifestyle and weight.
OR 6.1~6.9% proceed to FPG FPG ≤ 6.0 mmol/L Repeat test in 3 yrs
or OGTT OR
Age ≥ 40 2hOGTT < 7.8 mmol/L

FPG 6.1~6.9 mmol/L Pre-diabetes

OR : manage as per
2hOGTT 7.8~11.0 mmol/L ACG

FPG ≥ 7.0 mmol/L Diabetes

OR : manage
2hOGTT ≥ 11.1 mmol/L accordingly

7.0% and high probability no further tests needed

above of diabetes
 Concept Explanations & Details

DM Complications - retinopathy, blindness (microvascular)

- nephropathy, kidney failure (microvascular)
- neuropathy, amputation (microvascular)
- increased CVD by 2~4 times (macrovascular)
- reduced life expectancy by 5~10 yrs

Screening Tests for DM Diabetic Retinal Photography (DRP)

: to test for diabetic retinopathy
- adults with T1DM: within 5 yrs after the onset of diabetes
- pt with T2DM: at the time of diabetes diagnosis
if no evidence of retinopathy for ≥ 1 annual eye exam and
glycaemia is well controlled sscreening q1~2y can be considered

Diabetic Nephropathy Test

: T1DM – first 5 yrs after T1DM diagnosis/ T2DM – when diagnosed
I. SCr and/or eGFR
II. Urine Albumin/Creatinine ratio (uACR)
measure of how much albumin is in a urine sample relative
to how much creatinine there is
OR
Protein-Creatinine ratio (uPCR)
to monitor progress of renal function and effectiveness of
interventions

Diabetic Foot Screening (DFS)

- advise pt to maintain optimal glycaemic control
- encourage smokers to quit
- regularly educate pt on good foot care and appropriate
footwear

Albuminuria Definition

annual screening of 1) SCr and/or eGFR and 2) uACR in all pt, or

uPCR if sig. level of proteinuria

Monitoring of CV risk
factors & DM
complications
 Concept Explanations & Details
A for outpatient
Glycaemic Goals

{
Eimyatierst >
:
7 8~ (0 8 ;
.

This excludes gestation DM which requires tighter control.

Individualised Glycaemic - general goal: < 7.0%

Targets - more stringent goal: 6.0~6.5%
- short disease duration
- long life expectancy
- no sig. CVD
- less stringent: 7.5~8.0%
- Hx of severe hypoglycaemia
- limited life expectancy
- advanced complications
- extensive comorb.

Therapeutic Management ● Pharmacolotherapy

of DM ○ oral glucose-lowering agnets
○ injectable drugs
■ insulin
■ non-insulin agnets
■ combi. therapy (insulin + non-insulin agent)
● Non-pharmacotherapy
○ therapeutic lifestyle change (TLC)
● Management of DM-related complications
○ ARB/ACEi
○ MRA
○ lipid-lowering agents

Antidiabetic Drug Classes Oral Glucose Lowering Agents (OGLA)

- biguanides - thizolidinediones
- sulfonylureas - alpha-glucosidase inhibitors
- meglitinides - SGLT2 inhibitors
- DPP4 inhibitors - oral GLP-1 receptor agonist

Injectable Drugs
- insulin - GLP-1 receptor agonist
- dual GIP and GLP-1 receptor agonist

Lactic Acidosis - Signs & Sx

: N&V, abdominal pain, shallow / laboured breathing, mental
confusion
- pathophysiology CL
: due to increased prod. or decreased LC of lactate due to
Metformin or hypoxic state
 Concept Explanations & Details

Summary of Non-insulin Antidiabetic Drugs

IC 12 – Diabetes Mellitus (2)
Concept Explanations & Details

Insulin Pharmacology : most effective – reduce HbA1c up to 2.5%

Indication
: treatment of all types of DM & drug of choice in gestation DM pt

MoA
a. glucose: facilitate glucose uptake in muscle & adipose tissue
b. fat: enhance fat storage & inhibit fat mobilisation
c. protein: increase prot. synthesis & inhibit proteolysis in
muscle tissue

Action
- pancreas
: insulin secretion
- adipocyte
: glucose transport, prot. synthesis, lipogenesis,
lipolysis
- muslce
: glucose transport, glycogenesis
- liver
: gluconeogenesis, glycogenesis, glycogenolysis

PKPD
- response to insulin highly variable bet. individuals
- blood stream distributed directly after SC admin
- metabolism
: exogenous – mainly renal, endogenous – mainly hepatic

Insulin Injecting Sites Needle Length

- pen needles = 4 mm
- syringe needles = 6~12 mm (for vials)

Gauge Size (needle thickness)

- 28, 29, 30, 31, 32 gauges 31 & 32 used most commonly
- higher the gauge, the finer the needle
pain but needle weakness & speed of injection

Insulin Injection Sites

- abdomen: 2-inch circle around the navel
- top and outer thighs: avoid bony area above knees
- outer upper arms: areas where fatty tissues are present
absorption vary by site of injection (fastest to slowest)
: abdomen > outer upper arms top and outer thighs buttocks
rotate sites to prevent lipohypertrophy

Insulin Vial Size & Stability

- common size
- U-100 = 100 units/1 mL of insulin, so each vial
contains 1,000 IU
- stability of Insulin Rule of Thumb
 Concept Explanations & Details

: unopened insulin vials good until expiration date only if

stored in refrigerator (if x refrigerated, good for 28 d)
- opened = good for 28d regardless of refrigeration

Injection Skills Insulin Dose Preparation

1. Check insulin label for insulin type & expiration date
2. visually inspect the vial for contamination / degradation (e.g.
white clumps or colour change)
3. for all cloudy insulins, roll the vial gently back and forth bet.
hands to warm up
4. wipe top of vial & injection site with alcohol swabs
5. remove protective covering over the plunger & needle
6. draw up air equal to the insulin dose to be admin. into syringe
7. inject air into insulin vial
8. with the syringe still inserted, invert the vial & withdraw the
insulin dose
9. if bubble present, gently & remove the syringe from vial

SC Injection Technique
1. pinch the area to be injected
2. insert the needle at 90° angle to the centre of pinched area
3. press plunger to inject insulin
4. hold the syringe or device in the aea for 5~10 sec to ensure
full delivery of insulin
5. remove the syringe or device
6. release the pinch

Factors affecting Insulin ● temperature

Absorption ● massage
● exercise
● lipohypertrophy
: bulging of adipose tissue due to not rotating injection sites
can decrease insulin absorption
● others
: e.g. needle / gauge size, admin. technique, insulin
preparations, mixtures, conc., dose, insulin stability

Types of Insulin

- ultra-short acting - long-acting

- rapid-acting - ultra-long acting
- short-acting - others (e.g. mixed insulin)
- intermediate-acting

Category Insulin Target BG Onset Duration

Rapid Aspart (Novorapid) PPG 5~15 min 3~5 hrs

Lispro (Humalog) 1 injection/meal
Glulisine (Apidra)

Short Regular (Actrapid) PPG 30~60 min 6~8 hrs

1 injection/meal
 Concept Explanations & Details

Intermediate NPH (Insulatard) FPG 6~12 hrs 10~16 hrs

2 injection for 24 hr coverage

Long Detemir (Levemir) FPG 0.8~2 hrs ~24 hrs

Glargine U-100 1.5 hrs 1 injection for 24 hr coverage
(Lantus) (Lantus)
- for intermediate- and long-acting insulin, inject regardless of meal timings, at the same
time of the day

Ultra-long acting Insulin

: appears to have lower rates of hypoglycaemia than Glargine (U-100) due to more gradual release
of insulin
1. Insulin Degludec (Tresiba)
: peakless with DoA of 42 hrs
inject SC OD at any time of the day
2. Insuline Glargine U-300 (Toujeo)
: peakless with DoA 36 hrs
inject SC OD at any time of the day

Mixed Insulin Self-mixing

- stable mixes
: after mixing, need to administer within 15 mins before it
becomes unstable
- Regular + NPH
- Rapid-acting + NPH
- unstable mixes
- Glargine + other Insulins ( incompatible pH)
- Glulisine + Insulins other than NPH ( x compatible)
- Detemir + other Insulins ( x recommend by
manufacturer)
when mixing, draw clear insulin first, then draw cloudy insulin to
avoid contamination risk

Pre-mixed s all pre meal

-

Generic Onset Duration Administration

Novomix 30 10~20 mins 18~24 hrs 15 mins before

(30% Aspart + 70% meal
Aspart protamine)

Humalog Mix 75/25 15~30 mins 14~24 hrs

(25% Lispro + 75%
Lispro protamine)

Humalog Mix 50/50 15~30 mins 14~24 hrs

(50% Lispro + 50%
Lispro protamine)

Mixtard 70/30 30 mins 2~12 hrs 30 mins before

(70% NPH + 30% meal
Regular)
 Concept Explanations & Details

Considerations about PO Therapies when Injectables Initiated

: 1) if increasing Insulin secretion discontinue, 2) if increasing
Insulin sensitivity continue.
a. Metformin (insulin sensitiser) continue
b. TZDs discontinue or reduce TZD dose
: TZD is insulin sensitiser, but study results show that it
increases risk of hypoglycaemia
c. SUs (increase insulin secretion) discontinue or reduce SU
dose byo 50% when∞ basal insulin initiated Glargine
T
,
Dethopir

Deglandee
.
,

d. SGLT2 inhibitors continue (targets kidneys & has CV-renal

benefits) " =
nglutiales
e. DPP4 inhibitors discontinue if GLP-1 agonist initiated

Insulin Dosing General Rule of Thumb

Conversion : most Insulin conversions are at 1:1 unit
…

reduce dose by 10~20% if pt at high risk of hypoglycaemia

Exceptions (MUST decrease dose)

- BD NPH to OD Glargine U-100 / Detemir
decrease byDxosuid
20%
e.g. 20 IU NPH BD 32 IU Glargine U-100 OD
- Glargine U-300 to other basal Insulin analogue Glargine0s - 100 & Bathonir

decrease by 20%
e.g. 40 IU Glargine U-300 32 IU Glargine U-100 /
Detemir

ADR Hypoglycaemia
: BG ≤ 3.9 mmol/L
- Sx: blurry vision, sweating, tremor, hunger, confusion,
anxiety, shaking, tachycardia, dizziness, weakness & fatigue
- nocturnal Sx: nightmares, restless sleep, profuse sweating,
morning headache
- management
: 15-15-15 rule
15 g of fast-acting carbohydrates wait 15 mins check
BG and take another 15 g if still BG < 3.9 mmol/L
commonly found fast-acting 15 g CHO
: fruit juices, raisins, sugar, hard candies, regular soft drinks,
honey avoid those with high fat & protein ( can increase
insulin secretion)

Weight Gain
: more than pt on SUs
benefits of glycaemic control outweighs weight gain

Lipohypertrophy
: bulging of adipose tissue due to not rotating injection sites

Local allergic Rxn

: redness, swelling and itch at injection site
only for protamine-conatining insulin products. x observed in
 Concept Explanations & Details

protamine-free formulations

Dosing Normal Circumstance

: initiate with basal FPG control
10 IU NPH at bedtime or 0.1~0.2 IU/kg/d (preferred)
Glargine / Determir / Degludec
4. 0 n . mmold

Dftarget
: 7
0

HbA1c Uncontrolled, continue to act on FPG

: increase insulin 2 IU q3d until FPG at goal
may increase 4 IU q3d if FPG consistently > 10 mmol/L
reduce insulin by 10~20% if no clear reason for hypoglycaemia

HbA1c still above goal despite basal dose 0.5 IU/kg OR FPG at
goal
1) add prandial coverage (rapid / regular) gradually
- 1 dose with largest meal
- 4 IU or 10% of basal
- if HbA1c < 8%, decrease basal dose by 4 IU or 10%
_

2) if on bedtime NPH
- consider splitting dose into 2 doses
⅔ in AM (breakfast + lunch), ⅓ in PM (dinner)
m _

Stopping Increase
: stop basal insulin dose increase once > 0.5 IU/kg
overbasalisation
^
basal insulin has ceiling effective dose where FBG reduction
become proportionally smaller with increasing dose
potential consequence if not stopped weight gain,
hypoglycaemia, post-prandial hyperglycaemia

Eventually pt will have multiple Insulin dose

: basal usually consist of 50% or more of total daily dose
1) full basal-bolus regimen
- 1 injection of basal + 3 injections of Regular / Rapid
for each meal
- 4 injections daily
2) BD pre-mix regimen (preferred)
- Intermediate + Regular / Rapid (Mixtard or Novomix)
- 2 injections daily
IC 13 – Diabetes Mellitus (3)
Concept Explanations & Details

Diabetic Emergencies : diabetic ketoacidosis (DKA) & hyperglycaemic hyperosmolar state

(HHS) = serious acute metbaolic complications of DM with high
mortality rate
- results from absolute / relative insulin deficiency
: stimulate lipolysis circulating FFA [O] to ketone
bodies which is strong acid causing metabolic acidosis
- stress stimulates insulin ‘counter-regulatory’ hormones (e.g.
glucagon, catecholamines, GCs, GH)
gluconeogensis, peripheral insulin sensitivity and
hyperglycaemia by increasing insulin resistance
most common underlying cause = infection
other causes: e.g. MI, stroke, inadequate insulin, pancreatitis
management: restoration of hypovolaemia,
_
correction of
hyperglycaemia,
mmmmmmmm
ketogenesis, electrolyte imbalanace, treatment of
precipitating factors ( )
IV continuous insulin infusion admin. until DKA/HHS revolve
then transit to SC insulin therapy

Diabetic Ketoacidosis (DKA)

: more common in T1DM than T2DM
- characteristics: fruity breath odour, acidosis
- may be a bit drowsy, but usually still alert
mn

- BG > 14 mmol/L

Hyperglycaemic Hyperosmolar State (HHS)

: observed in T2DM
- usually no ketones as there is still residual insulin
- usually extremely dehydrated hence BG can be > 33 mmol/L
- usually stupor
~

Somogyi Efffect vs : common to have high BG levels at dawn, which can be explained by
Dawn Phenomenon the following two therories
so good to check BG level around 2~3 am

Dawn Phenomenon
: release of cortisol in the waking hours causes BG levels to rise
sharply
between 4~8 am
for normal person, insulin is secreted accordingly but x in diabetic
pt end up hyperglycaemic

Somogyi Effect
: BG levels drop sharping at night (e.g. miss bedtime snack / too
much insulin) body responds by releasing glucagon which
increases BG level

Newly Diagnosed DM Initiation

Management - Metformin = preferred option for T2DM & shld be continued
as long as possible if no C/I
- combi. therapy can be considered if HbA1c quite elevated
 Concept Explanations & Details

- choice of agents depends on goal of therapy, usually pt’s

cardio-renal risk

Hx of ASCVD, HF or CKD
: consider independently of HbA1c to ~add
- ASCVD = GLP-1 agonist or SGLT2 inhibitor
- HF = SGLT2 inhibitor
- CKD = SGLT2 inhibitor preferred over GLP-1 agonist
(if pt already showing hyperalbuminuria or eGFR < 60)

HbA1c still above target after adding Metformin

- need for glucose-lowering efficacy
: Insulin, certain GLP-1 agonist and combi. therapy highest
- need to minimise hypoglycaemia (e.g. elderly)
avoid SU, Insulin
- promote weight loss GLP-1 agonist, SGLT2 inhibitor

BP Management in : BP < 130/80 mmHg recommended to 1) reduce CVD mortality and

Diabetes 2) slow CKD progression
ACEi / ARB = preferred 1st-line agents

Lipid Management in : for those 40~75 yo moderate-intensity statin therapy

Diabetes – 1° Prevention - Atorvastatin 10~20 mg / Rosuvastatin 5~10 mg /
Simvastatin 20~40 mg
consider high-intensity statin if additional ASCVD risk factor
target LDL-C reduction of 50% from baseline & < 70 mg/dL (1.8
mmol/L)

Lipid Management in : for those with ASCVD high-intensity statin therapy

Diabetes – 2° Prevention - Atorvastatin 40~80 mg / Rosuvastatin 20~40 mg
target LDL-C reduction of 50% from baseline & < 55 mg/dL (1.4
mmol/L)
addition of Ezetimibe or PCSK9 inhibitor recommended if goal x
achieved

Role of Antiplatelet Agent Aspirin as 1° Prevention for…

in Diabetes - age ≥ 50 yo
- diabetic
- ≥ 1 additional major risk factors
: LDL-C ≥ 2.6 mmol/L, HTN, smoking, CKD, albuminuria,
family Hx of premature ASCVD

Aspirin as 2° prevention for…

- diabetic
- Hx of ASCVD
Clopidogrel (75 mg/d) may be used if allergic to Aspirin

CKD in Diabetes Clinical Presentation of Diabetic Kidney Disease (DKD)

- presence of albuminuria without gross haematuria
- x S&Sx of other primary causes of kidney damage
- other considerations
: long duration of diabetes, presence of retinopathy (esp.
 Concept Explanations & Details

T1DM – DKD may be present in T2DM without retinopathy),

gradual decrease in eGFR

Recommended Agents
1. ACEi / ARB
: recommended for pt with micro- or macroalbuminuria
reduces kidney disease progression & CV events
titrate to max. tolerated dose
2. SGLT2 inhibitor
: for T2DM + DKD + eGFR ≥ 20 for Empa., ≥ 25 for Dapa.
reduces kidney disease progression & CV events
use concurrently with ACEi / ARB

Finerenone : MRA with no anti-HTN effect. For those who can’t tolerate SGLT-2i
- indication
: slow CKD progression, reduce kidney failure risk, HA, HF
hospitalisation and CV death in adult pt with CKD assc. with
T2DM
- S/E
: hyperkalaemia, hypotension, lower risk of gynaecomastia
compared to Spironolactone
- useful for those with eGFR > 25

Preventive Immunisations : diabetic pt have higher risk of infection

in Diabetes - Influenza vaccine (annually)
- COVID-19 vaccine
- Pneumococcal polysaccharide vaccine
- Hep B vaccine
- Shingles (Herpes Zoster) vaccine
- Respiratory syncytial virus vaccine
- Tetanus, Diphtheria, Pertussis (Tdap) vaccine

Continuous Glucose : measures interstitial glucose

Monitoring (CGM) benefits
- improvement in HbA1c reduction
- reduction in hypoglycaemia

Concept of Glucose : Time-In-Range (TIR)

Variability 70% TIR aligns with an HbA1c of 7%
TIR correlates with risk of complications