Mr. MK, a 55-year-old man, has poorly controlled type 2 diabetes and hypertension despite being on metformin, gliclazide, and amlodipine for 10 years. He is non-compliant with his diet and medications due to his frequent travel for work. Examination found proliferative retinopathy, obesity, and elevated A1c and blood pressure. Treatment recommendations included adding a GLP-1 receptor agonist or SGLT2 inhibitor, continuing metformin, adding irbesartan to target a blood pressure below 135/75 mmHg, and addressing non-pharmacological factors like diet, exercise, and weight loss.

1. Case Study:
Hypertension
and
Diabetes

2. Case
Mr. MK, a 55-year-old man.
T2DM and hypertension for 10 years. Medications:
Metformin 1 g bd
Gliclazide 160 mg bd
Amlodipine 10 mg daily
Referred for further management of poorly controlled
diabetes and hypertension.

3. What are the possible causes for his poorly
controlled diabetes and hypertension?
• Non-compliant to diet
• Non-compliant to treatment
• Hypoglycaemia?
• Underlying infections?
• Silent ischaemia?

4. • Social history: Salesman
Frequent travelling
On and off missed his medications
Diet not controlled
• Family history: Mother – diabetic, on dialysis
Father – stroke (residual left hemiparesis)

5. On examination:
• Obese
• Weight 98 kg, BMI 35 kg/m2
• BP 160/90 mmHg
• PR 88 beats/minute
• Bilateral proliferative retinopathy
• Minimal bilateral leg oedema
• Other systemic examination: unremarkable

6. 9.2 %
11.8 mmol/L
106 μmol/L
Investigation results:
• A1c
• FBS
• Creatinine
• e-GFR 88 ml/min/1.73 m2
• 24h urinary protein 200 mg/24h
• ECG LVH

7. What are the issues that need to be addressed?
1. Poorly controlled diabetes with presence of microvascular
complications
2. BP level not to target
3. Obesity could contribute to the poorly control diabetes and
HPT
4. Need to explore any morbidities associated with the
obesity (sleep apnoea, fungal infections etc)

8. Questions
What would be the A1c and BP target?
How would you manage him?
What would be the choices of anti-hypertensives or anti-
diabetic agents?

9. Glycaemic Control
• TargetA1c: ≤ 6.5%
• Add GLP1-receptor
agonist or SGLT2-
inhibitor
• Continue Metformin
Blood Pressure Control
• Target BP ≤ 135/75 mmHg
(based on ADVANCE ON
trial)
• Pharmacological approach:
– add ARB: Irbesartan 150 mg
daily (renoprotection)
• Non-pharmacological
approach
– sodium restriction
– exercise
– weight loss

10. ADVANCE-
post trial ObservatioNal Study
BPArm Results

11. Flow-chart for BP arm
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11,140 underwent randomisation into
the blood pressure control arm
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• •
5,569 assigned to Active 5,571 assigned to Placebo
408 patientsdied r- -I 471 patients died
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5,161 eligible fo r ADVANCE-ON 5,100 eligible fo r ADVANCE-ON
+-
88non-part.icipating
patientsand sites
-884 non-park
t ipating
patients and sites
4,278 participated in
ADVANCE-ON
4,216 participated in
ADVANCE-ON
-
592 died
1,048 nofinal visit
623 die d
1,100 no final visit
2, 638atfinal visit,2013 2,493 at final visit, 2013
N=l l,140
(100%)
N=l0,261
(92%)
N=S,494
(83%of those
stillalive)
N=S,131
(70% ofthose
still alive in
2013)

12. BP levels: in-trial and post trial
(before and after stopping randomised treatment)
BP arm BP level (mmHg)
Mean
Active Placebo
Pre-randomization 145/81 145/81
Last randomized visit (after median of 4.4 years) 136/74 140/75
First ADVANCE-ON visit (a further 2.9 years later) 137/75 137/75
Final ADVANCE-ON visit (a further 3 years later) 137/74 138/75

13. Effects on M ortality
AHcause mortality Cardiovascular death
10
10
-
- Placebo
Perindopril-indapamide -- Placebo
Perindopr il-indapamide
-
'if!.
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u Relative risk reduction 14%;
p
: 0.025
0
0 6 12 18 24 30 36 42 48 54 60
Follow-up (months)
Relativerisk reduction 18%;
p=0.02 7
0
0 6 12 18 24 30 36 42 48 54 60
Follow-up (months)
Patel, MacMaho n, Chalmers et al. Lancet 2007;370:829-840

14. Up to 5
weeks
Screening/Enrollment
Irbesartan 150 mg*
Irbesartan 300 mg*
Follow-up: 2 years
Control group*
IRMA 2 Study Design
• 590 patients with hypertension, type 2 diabetes,
microalbuminuria (albumin excretion rate 20–200 µg/min),
and normal renal function
Double-blind Treatment
* Adjunctive antihypertensive therapies (excluding ACE inhibitors, angiotensin II receptor antagonists, and
dihydropyridine calcium channel blockers) could be added to all groups to help achieve equal blood pressure
levels.
Parving H-H, et al. N Engl J Med 2001;345:870-878.

15. 10
5
0
15
20
0 3 6 12 18 22 24
Follow-up (months)
Subjects
(%)
Control
Irbesartan 150 mg
Irbesartan 300 mg
IRMA 2 Primary Endpoint
Time to Overt Proteinuria
Parving H-H, et al. N Engl J Med 2001;345:870-878.

16. 14
18
16
12
10
8
6
4
2
0
Subjects
(%)
Control
(n=201)
150 mg
(n=195)
300 mg
(n=194)
Irbesartan
9.7
5.2
14.9
RRR=39%
P=0.08
RRR=70%
P<0.001
IRMA 2 Primary Endpoint
Development of Overt Proteinuria
Parving H-H, et al. N Engl J Med 2001;345:870-
878.

17. IRMA 2
Normalisation of UAE Rate
35
45
40
30
25
20
15
10
5
0
Subjects
(%)
Control
(n=201)
150 mg
(n=195)
300 mg
(n=194)
Irbesartan
24
34
21
P=0.006
Parving H-H, et al. N Engl J Med 2001;345:870-878.

18. Table 8 (A): Choice of antihypertensive drugs in diabetes patients with
concomitant conditions (Adapted from Malaysian CPG for Hypertension 2008)
Concomitant
Disease
Diuretics -blockers ACEIs CCBs
Peripheral
-blockers
ARBs
DM (without
nephropathy) + +/- +++ + +/- ++
DM (with
nephropathy) ++ +/- +++ ++* +/- +++
Gout +/- + + + + +
Dyslipidaemia +/- +/- + + + +
Coronary
heart disease + +++ +++ ++ + +
Heart failure +++ +++# +++ +@ + +++
Grading of recommendation (+) to (+++) is based on increasing levels of evidence + current widely accepted practice
+/- Use with care
- Contraindicated
* Only non-dihydropyridineCCBs
# Metoprolol, bisoprolol, carvedilol – dose needs to be gradually titrated
@ Current evidence available for amlodipine and felodipineonly

19. Take Home Messages
• TargetA1c ≤ 6.5%
• Target BP ≤ 135/75 mmHg
• Most patients with hypertension will require two or more
antihypertensive agents to achieve their BP goals
• Pharmacological treatment should comprise a regimen
that includes either an ACEI or an ARB as first line.