1. Anti-diabetic therapy
Early Experience with Dapagliflozin in the Management of
Patients with Type 2 Diabetes in MOH Hospitals in Malaysia
Zanariah Hussein 1, Mohd Badrulnizam Long Bidin 2 , Norazizah Aziz 3, Ijaz H Rahmatullah 4,
Norhaliza M Ali 5, Norshaffinaz A Merican 6, Foo Siew Hui 7, Norhayati Yahaya 8,
Yong Sy Liang 9, Florence Tan 10, Masni Mohamad 1, Nurain M Noor1, Anilah A Rahim4
Endocrinology Units , Medical Departments, 1Hospital Putrajaya, 2Hospital Kuala Lumpur, 3Hospital Pulau Pinang,
4Hospital Raja Permaisuri Bainun Ipoh, 5Hospital Sultanah Aminah Johor Baru, 6Hospital Sultanah Bahiyah Alor Setar, 7Hospital Selayang,
8Hospital Raja Perempuan Zainab II Kota Baru, 9Hospital Tengku Ampuan Rahimah Klang, 10Hospital Umum Sarawak
AFES 2015, KL
P 38
INTRODUCTION
SGLT2-Inhibitors are a new class of oral antidiabetic (OAD) therapy which lower blood glucose by inhibiting renal tubular glucose reabsorption, thus promoting urinary glucose excretion. The associated caloric deficit together with fluid loss via osmotic diuresis commonly leads to weight loss and improvements in blood pressure as evidenced in randomised clinical trials. Hypoglycaemia risk is minimal with these medications as they act via an insulin-independent mechanism. Therefore they represent an ideal approach to managing patients with Type 2 diabetes (T2DM) – addressing the composite targets of lowering hyperglycaemia, promoting weight loss and minimising hypoglycaemia.
Safety concerns include hypovolemia, dehydration and postural hypotension as a result of osmotic diuresis, particularly in the elderly and those on diuretic therapy. There is increased rates of urinary and genital tract infections, particulaly in females and recently there has been some concern on potential skeletal effects such as bone loss.
These class of agents may be used as monotherapy, as add-on therapy in dual/ triple OAD therapy and insulin therapy as seen in clinical trials and recently have been recommended as an early option of therapy for patients with T2DM in most international treatment algorithms, particularly favoured in those patients who are overweight or obese, It is restricted in patients with renal impairment and avoided if eGFR < 60 ml/min. There are currently three different agents approved by US FDA – dapaglilozin, canagliflozin and empagliflozin. Dapagliflozin is currently the only SGLT-2 inhibitor registered for use in Malaysia since We reviewed the clincial experience with dapagliflozin, prescribed by endocrinologists in a few Ministry of Health hospitals in Malaysia.
OBJECTIVE
METHODOLOGY
To assess the safety and efficacy of dapagliflozin as add- on therapy in patients T2DM in MOH hospitals in Malaysia.
In particular, to assess
Weight effects
HbA1c effects
Blood pressure effects
Hypoglycaemia
Urinary and genital tract infections
We performed a retrospective review of all patients with Type 2 diabetes that were initiated on dapagliflozin since it was first introduced in Malaysia. This study was registered and approved by the National Medical Research Registry (NMRR).
Currently, dapagliflozin is not listed in the Ministry of Health (MOH) Drug Formulary and it’s prescription by MOH endocrinologists using the hospital medication budget is allowable but restricted to individuals on a “named patient” basis having prior approval by the Director General of Health. Very few patients are purchasing the medications on their own due to its comparatively high cost.
Data reporting forms were distributed to all MOH endocrinologists who had prescribed dapagliflozin in their centre since Data collected included demographic data, duration of diabetes, baseline GFR, baseline and follow-up HbA1c, weight and blood pressure, present of adverse effects in particular hypoglycaemia, hypovolemia and urinary tract infections (UTI) or genital tract infections (GTI). All patients prescribed dapagliflozin were included, regardless of duration of treatment.
RESULTS
Ninety patients from 11 different MOH hospitals were initiated on dapagliflozin since May 2014, prescribed by endocrinologists (Table 1).
Baseline characteristics of patients were as follows
Mean age was 48.3 years (range 23 – 76 years). Seven patients (7.7%) were of elderly age (> 65years). Gender distribution % males, % females
Mean baseline weight was 92.3 kg (range 57 – 155kg)
Mean duration of T2DM was 10.3 yrs (range 1 – 29yrs). 44 patients (48.9%) had T2DM > 10 years.
Baseline anti-diabetic therapy is shown in Table 2. Majority of patients were on metformin, sulphonyurea, DPPIV-inhibitor and insulin therapy. In 90%, dapagliflozin was added on as third or forth-line therapy.
Mean baseline HbA1c was 9.1% (range %). 41 patients (45.6%) had baseline HbA1c > 9%
Sixty patients (66.7%) had hypertension, 6 patients were on diuretics.
Mean blood pressure was 137/77 mmHg
Effects of treatment with dapagliflozin
Mean duration of therapy with dapagliflozin was 6.4 months.
HbA1c change (Table 3) : Almost 70% experienced HbA1c reductions of at least 0.4% (range 0.4 – 5.0%). Mean HbA1c reduction was 1.0%.
Weight change (Table 4) : The majority of patients experienced weight reduction, ranging between 0.5 – 10.3 kg with mean weight loss of 2.8kg.  Among those with weight loss, 63% experienced more than 2kg loss.
Blood pressure was reduced in almost 40%, unchanged in 47%.
No reported side effects in 82.2% of patients. UTI / GTI occurred in 4 patients (4.4%) with one case of combined infection. Of those with hypoglycaemia, three patients were on insulin and one on sulphonylurea (Table 5).
Fifteen patients (16.7%) discontinued dapagliflozin, mainly due to noncompliance and nonresponse (Table 6).
Table 1: Distribution of patients from MOH hospitals
Table 2: Type and no. of baseline antidiabetic therapy
Anti-diabetic therapy
No. of pts (%)
Metformin
Sulphonylurea
Thiazolidinedione
DPPIV-Inhibitor
Acarbose
GLP-1 RA
Insulin
No. of baseline medications
No therapy
Single therapy
Dual therapy
Triple therapy
89 (98.9)
17 (18.9)
5 (5.6)
22 (24.4)
1 (1.1)
49 (54.4)
8 (8.9)
63 (70)
18 (20)
Table 3: HbA1c change on dapagliflozin
Table 4: Weight change on dapagliflozin
HbA1c change
HbA1c range (%)
No. of patients (%)
N= 75
Reduction (0.4 % or more)
- 0.4 – 1.0 %
- 1.1 – 2.0 %
- > 2.0 %
No change ( %)
Increase (0.4 % or more)
0.4 – 5.0
0.4 – 2.2
52 ( 69.3)
23 (44.2)
21 (40.4)
8 ( 15.4)
11 ( 14.7)
12 ( 16.0)
Weight change
No. of pts (%)
N= 75
Reduction (0.5kg or more)
- 0.5 – 2.0 kg
- 2.1 – 5.0 kg
- > 5.0kg
No change ( kg)
Increase (0.4kg or more)
59 ( 78.7)
22 ( 37)
27 (46)
10 (17)
6 ( 8.0)
10 ( 13.3)
Table 5: Adverse effects while on dapagliflozin
Table 6: Reasons for discontinuation of dapagliflozin
Adverse effects
No. of patients (%)
Urinary Tract Infection
Genital Tract Infection
Volume depletion
Hypoglycaemia
Others – biliary colic
3 ( 3.3)
2 ( 2.2)
1 ( 1.1)
4 (4.4)
1 (1.1)
HbA1c change
No. of patients
Noncompliance
Nonresponse
Adverse effects
- UTI/ GTI
- Hypovolemia
- Biliary colic
Others (eg. financial constraint) 4 5 2 1
DISCUSSION
Many patients with T2DM remain in poor glycaemic control despite multiple anti-diabetic therapies. Endocrinologists in MOH hospitals in Malaysia prescribed dapagliflozin, an SGLT-2 inhibitor, mainly as add-on therapy in combination with metformin, insulin and/or DPPIV- inhibitors. The majority of patients initiated on dapagliflozin achieved reasonable improvement in HbA1c, along with weight reduction and treatment was well tolerated. Adverse effects were minimal with UTI / GTI occurring in less than 5% of patients and less than 5% discontinued dapagliflozin due to adverse effects.