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CLINICAL CASE IN DIABETES

CASE 1

Renoprotective role of Gliclazide MR 60 mg


in the context of multiple risk factors
for cardiovascular disease.
CASE HISTORY

52-year-old female
Postmenopausal - osteoarthritis of the knees

Family history of type 2 diabetes

Sedentary

Smoker - no alcohol
CASE HISTORY
Two months earlier, emergency hospital admission for
suspected acute coronary syndrome (ACS)

Diagnoses made:
No stenotic lesions
Type 2 diabetes
Mixed dyslipidemia
Hypertension

Consultation for:
Intermittent malaise for a month
Recurrent vulvovaginitis
MEDICATIONS

Her medication included:


Metformin 500 mg bd
Atorvastatin 10 mg/day

Fenofibrate 160 mg/day

Combination of perindopril 2.5 mg + indapamide


0.625 mg
Aspirin 75 mg

Paracetamol
CLINICAL EXAMINATION
BMI: 30 kg/m 2

Waist circumference: 88.2 cm


No signs acanthosis nigrans
Blood pressure: 170/85
Cor : No cardiac decompensation, HR : 84p/m, regular
Lungs : No rales, no abnormality found
Abdomen : Supple, no organo-megaly
Normal ankle reflexes
Minor vision loss, Minor bilateral background
retinopathy
Presence of vulvar candidiasis
LABORATORY INVESTIGATION
Renal function:
eGFR: 55 mL/min/1.73m2
Macroalbuminuria: 897 mg/g
Kidney: normal size

Urinary test:
No bacterial urinary infection

Glycemia:
HbA1c: 8.3%
LABORATORY INVESTIGATION
Lipid profile:
HDL cholesterol: 42.4 mg/dL
LDL cholesterol: 208.4 mg/dL
Triglyceride: 92.6 mg/dL

Liver function:
ALAT: 59 IU/L

Thyroid function:
Normal
LABORATORY INVESTIGATION

Cardiovascular function:
Sinus rhythm

No evidence of ischemia

No evidence of left ventricular hypertrophy


DIAGNOSIS - PROGNOSIS
Q1: If patient came to you 10 years ago, What is the main
consideration for the risk factors from cardiovascular?

Answer:
1) . BMI
2) . Blood Pressure
3) . Post Prandial Blood Glucose
4) . Albuminuria
5) . Smoking habit
DIAGNOSIS - PROGNOSIS
Q2: Beside the blood glucose, what is your main priority to treat first?

Answer:
1) . Blood Pressure
2) . Pulse pressure
3) . LDL-cholesterol
4) . Smoking habit
5) . None above
DIAGNOSIS - PROGNOSIS
Q3: To treat your type 2 diabetes patients, what is the main level success of
the treatment?

Answer:
1) Body weight reduction
2) HbA1c
3) Micro-macro albuminuria reduction
4) Fasting blood glucose
5) Post-prandial blood glucose
DIAGNOSIS - PROGNOSIS
Q4: In doing aggressive treatment, which risk factor that would be your first
consideration?

Answer:
1) Fasting blood glucose as pre-diabetic state
2) A 4-year duration of diabetes
3) Life expectancy
4) A 30-year duration of diabetes
5) None above
THERAPEUTIC STRATEGY
Q5 : In your opinion, what is the most suitable
therapeutic strategy for this patient?

Answer:
1. Gliclazide MR 60 mg alone od
2. Gliclazide MR 60 mg plus DPP4i
3. DPP4i plus Metformin 500 mg TID
4. Metformin 500 mg plus Gliclazide MR 60 mg
5. Gliclazide MR 60 mg plus basal insulin
CASE 2
PATIENT WITH DIFFICULTY ACHIEVING
GLYCEMIC CONTROL
CASE 2

40-year-old woman
11-year history of type 2 diabetes (T2D)
(1rst consultation 2 years ago)
Positive family history of T2D (her mother)
Previous medications (several years):
metformin 850 mg twice daily
glipizide 5 mg twice daily
Unsatisfactory glycaemic control despite her compliance with
medications as well as lifestyle and dietary restrictions.
(very strict carbohydrate diet)
No history of hypoglycemia
CASE HISTORY
1 month before, switch from glipizide to vildagliptin 50 mg
June 2009 Aug 2010 Sept 2010

HbA1c 8.9 % 8.7 % 9.9 %

Fasting plasma
glucose - 13.1 13.0
(mmol/L)

Glipizide 5 mg BD Glipizide 5 mg BD Vildagliptin 50 mg BD


Medication
Metformin 850 mg BD Metformin 850 mg BD Metformin 850 mg BD

Worsening glucose control


fasting glucose ranging from 10 13.0 mmol/L
postprandial glucose 13.0 16.0 mmol/L
Endocrine consultation
PHYSICAL EXAMINATION
Height: 154 cm
Weight: 42.0 kg
BMI = 17.7 kg/m2
Waist circumference = 69.0 cm

Pulse 80/minute.
Blood pressure 110/80 mmHg.

Normal cardiovascular, respiratory and abdominal systems


Peripheral pulses well felt. Peripheral nerves intact.
Fundal examination, minimal background diabetic retinopathy.
CLINICAL INTERPRETATION
Common features noted in Asian patients with T2D:
(mentioned by Yoon KT et al1 and in the Asia-Pacific Cohort Studies Collaboration report2)

young-onset
low body mass index
Difficulty achieving glycemic control despite maximal oral
sulfonylurea and metformin therapy.
Switching her from oral glipizide to vildagliptin resulted in loss of
glucose control.
No past history of severe loss of glycaemic control suggestive of
diabetic ketoacidosis.
THERAPEUTIC DECISION AND STRATEGY
Q1. Is this young woman a candidate for insulin?
Answer:
1. Yes
2. No
3. I dont know
THERAPEUTIC DECISION AND STRATEGY
Patients desire for a trial of oral therapy:
Addition Gliclazide MR 60 mg daily

2 weeks later (October), improvement in glucose


control.
Consultation in December 2010:
-HbA1c = 7.0%
-Fasting plasma glucose = 6.7 mmol/L
-SMBG
Fasting plasma glucose = 5.8-7.7 mmol/L
Postprandial glucose = 5.7-11.5 mmol/L
-Well-being reported by the patient
PROGRESS AND FOLLOW-UP
Stable weight: 42-46 kg

Blood pressure: 100/80 mm Hg.

Non proliferative diabetic retinopathy

Normal biochemistry and lipids


Urine ratio microalbumin/creatinine <0.7 mg/mmol
(normal <3.5 mg/mmol).
PROGRESS AND FOLLOW-UP
Mar 2011 Oct 2011 Feb 2012 May 2012
HbA1c 6.2% 6.4% 6.7% 6.9%
Fasting plasma
glucose 6.7 8.3 7.9 -
(mmol/L)

Gliclazide MR 60mg Gliclazide MR 60 mg Gliclazide MR 60 mg Gliclazide MR 90 mg


Medication Vilda Met Vilda Met Vilda Met Vilda Met
50/850mg BD 50/850 mg BD 50/850 mg BD 50/850 mg BD

Good response to triple therapy


- Good (gliclazide, metformin, DPP-4 inhibitor)
glycemic control
- No problems of hypoglycemia for the past 3 years
- No development of diabetic microvascular complications (apart from the
mild retinopathy presented with in 2010)
COMMENTARY
This patient illustrates the cell secretory dysfunction noted as a
significant pathophysiological component of Asian T2DM.3-5
Fukushima et al3 showed that there is a loss of up to 80% of -cell
function once overt T2DM occurs.

Failure of treatment with a metformin and oral DPP-4 inhibitor


therapy combination
Glycemic control achieved only after addition of Gliclazide MR
60 mg daily

The improvement in HbA1c exceeded that which would have


been predicted, from 9.9% 7.0%, and then further to 6.2%.
DISCUSSION

Q2. Is there a risk of pancreatic exhaustion


with Diamicron MR 60 mg?
Answer:
1. Yes
2. No
DISCUSSION
Glucose-dependent insulin secretion6

Gliclazide MR 60 mg induces insulin release when blood glucose increases and


reduces insulin release with decrease in blood glucose.
COMMENTARY
In the clinical case, the larger and better response to addition of
oral sulfonylurea therapy (Gliclazide MR) is probably explained by
relatively high degree of -cell dysfunction linked to the patient
profile (young-onset T2DM, low BMI of 17.7 kg/m2 ).

After 11 years of disease, satisfactory control with oral


antihyperglycemic agents
However insulin initiation may be required in the future as
there is a noticeable trend for increasing fasting glucose.
DISCUSSION
Q3. Is the risk of hypoglycemia
higher with Gliclazide MR 60 mg
than with other oral treatments ?

Answer:
1. Yes
2. No
DISCUSSION
Low risk of hypoglycemia demonstrated7,8
DISCUSSION
In the clinical case, there are not episodes of moderate or severe
hypoglycemia even at HbA1c levels well below 7.0%

Reinforce the findings of very low prevalence of


severe hypoglycemia in patients in the ADVANCE
trial (Action in Diabetes and Vascular disease: PreterAx and DiamicroN MR
Controlled Evaluation), which used gliclazide MR as the
sulfonylurea in the intensive arm.9
DISCUSSION
Even incretin-based agents can be used to replace the older
insulin-secretory agents, they are unable to address -cell
dysfunction.

Sulfonylureas (gliclazide MR) will remain important therapeutic


agents to help patients achieve glycemic goals without
significant hypoglycemia or weight gain.
QUESTION
Q4. What is the place of sulfonylureas in the management of
type 2 diabetes?

Answer:
1. First line treatment
2. Second line treatment
3. SU puts risk of pancreatic exhaustion
4. SU risks of hypoglycemia
5. I dont know
DISCUSSION
Sulfonylureas the first choice for Newly diagnosed
patients & uncontrolled by metformin10
Thank you

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