SGLT2 inhibitor -A boon in uncontrolled dm

A case of T2DM who is uncontrolled on Insulin
Managed with Dapagliflozin add on to Insulin
Dr NIRMAL JAISWAL MD(med)
Consultant Physician & ICU Director
Suretech Hospital
Nagpur – India
theintensivist@hotmail.com

Clinical
Presentation:
A 52-year-old obese
man
8- year history of type
2 diabetes
Generalized malaise
and loss of appetite
since 2 weeks
Medical
History:
Recently struggling to
achieve glycemic
targets
weight gain over the
past 5 years.
History suggestive of
episodes of
hypoglycemia
Family
History:
Diabetes mellitus,
Hypertension
Case Presentation

Clinical Presentation:
High grade fever X 5 Days
Increasing breathlessness 3 days
Cough with expectoration X 5days
Case Presentation

Past history
Hypertensive and
dyslipidemic since
past 3 years
Medication
History
Tab Metformin 1500
mg BD + Inj Insulin
Premix 70/30 35 IU BD
Tab Lisinopril 10 mg OD
for hypertension
Tab Atorvastatin 10 mg
OD for dyslipidemia
Family
History:
Mother was diabetic
and hypertensive
The patient does not follow any specific diet.
he rarely exercises due to fatigue and lack of energy
Case Presentation

• Obese,Weight: 79 Kg; Height: 162 cm; BMI: 30.1
Kg/m2; Waist circumference: 89 cm
• Fever:101 PR: 70/min , BP: 140/90 mmHg RR:
30 breaths /min ; Temperature: 100° F
General Examination:
•RS: Crepts and TBB at base rt LL.
•P/A: No hepatomegaly, No Spleenomegaly. Bowel
sounds heard.
•CVS: S1 and S2 heard, No added sounds
Systemic Examination:
On Examination

Clinical Investigations
No abnormality detected in electrocardiography
Parameters Values
Hemoglobin 11.1 g/dL
Fasting blood glucose 142 mg/dL
Postprandial blood glucose 296 mg/dL
HbA1c 8.9%
Serum creatinine 0.9 mg/dL
Blood urea nitrogen 17 mg/dL
Total cholesterol 275 mg/dL
Low density lipoprotein-cholesterol 189 mg/dL
High-density lipoprotein-cholesterol 35 mg/dL
Triglycerides 255 mg/dL
Serum electrolytes Normal
eGFR 75 mL/min/1.73 m2
CBC : 11,34,23400
LFT : NAD
X ray chest

Diagnosis
• Rt lower lobe pneumonia in a case of Uncontrolled diabetes,
uncontrolled dyslipidemia, hypertension, and obesity
Management
• Inj Amoxy-clav + IV clarithro
• What should be the choice of therapy for controlling DM in this
case scenario?
Diagnosis and Management Plan

Many good drugs are available but they have some
limitation particularly – in CKD,derranged LFT, obesity or
lead to weight gain
Choose A Safe drug
which will help in
preservation of
organs in a long run
which is a ultimate
goal of ours

Limitations with current oral glucose-lowering agents
Do newer agents address these limitations??
Fonseca, V., et al. Diabetes Obes Metab. 2011 Apr 11; DeFronzo RA. Ann Intern Med. 1999;131:281–303;
UKPDS. Lancet. 1998; 352:837–853; Aschner P, et al. Diabetes Care.2006;29(12):2632-7;
ADA and EASD Consensus statement. Diabetes Care. 2009;32:193–203; Nesto RW, et al. Circulation 2003;108:2941–
2948;
Matthaei S, et al. Endocrine Reviews. 2000;21:585–618; Raptis SA & Dimitriadis GD. J Exp Clin Endocrinol.
Drug/
Limitations
HYPO-
GLYCEMIA
WEIGHT
GAIN
CV RISK GI
SIDE
EFFECTS
RENAL
MONITORING &
DOSE
ADJUSTMENT
DRUG-DRUG
INTERACTIONS
HEPATIC
MONITORING
& DOSE
ADJUSTMENT
BP REDUCTION
METFORMIN
SUS
GLINIDES
TZDs
GLP-1 RECEPTOR
AGONISTS
INSULIN
DPP-4 I
AGIS
SGLT 2 INHIBITORS
Newer agents
Favourable
Judicious use
Cautiontheintensivist@hotmail.com

Dapagliflozin as add-on to insulin (± OADs):
Significant reductions in HbA1c sustained over 2 years1
Dapagliflozin is not indicated for the management of obesity.3 Weight change was a secondary endpoint in clinical trials.3,4
A multicentre, randomised, double-blind, placebo-controlled, parallel-group, 24-week study in patients with Type 2 diabetes with inadequate glycaemic
control (HbA1c 7.5–10.5%) on a stable dose of insulin ± up to two OADs. Primary endpoint: HbA1c reduction at 24 weeks.1 Data are adjusted mean
change from baseline estimated from a mixed model.
1. Wilding JP, et al. Diabetes Obes Metab 2014;16:124–36; 2. Wilding JPH, et al. Ann Intern Med 2012;156:405–15; 3. Dapagliflozin. Summary of
product characteristics, 2014; 4. Bailey CJ, et al. Lancet 2010;375:2223–33.
Dapagliflozin
also offers…
additional benefit
of weight loss
without the
need for
increased insulin
dosing
At 24 weeks, dapagliflozin was associated with HbA1c reductions of –0.96% versus –0.39% with
placebo (p<0.001)2

Significant weight loss sustained over 2 years1
Dapagliflozin is not indicated for the management of obesity.2 Weight change was a secondary endpoint in clinical trials.2,3
A multicentre, randomised, double-blind, placebo-controlled, parallel-group, 24-week study in patients with Type 2 diabetes with inadequate
glycaemic control (HbA1c 7.5–10.5%) on a stable dose of insulin ± up to two OADs. Primary endpoint: HbA1c reduction at 24 weeks.Data are
adjusted mean change from baseline estimated from a mixed model.
1. Wilding JP, et al. Diabetes Obes Metab 2014;16:124–36; 2. Dapagliflozin. Summary of product characteristics, 2014; 3. Bailey CJ, et al.
Lancet 2010;375:2223–33.
Reduction in Body weight
by 3.33 Kgs

Reduction in Insulin requirement
IU, International units.
1. Wilding JPH, et al. Ann Intern Med 2012;156:405–15; 2. Wilding JP, et al. Diabetes Obes Metab 2014;16:124–36.
Reduction in Insulin
requirement > 18 U

Reduction in albuminuria with Dapagliflozin in Patients With Type
2 Diabetes and Moderate Renal Impairment
CI=confidence interval; DAPA=dapagliflozin; PBO=placebo. Sjöström CD et al.
World Congress of Nephrology. March 13-17, 2015; Cape Town, South Africa. Poster SAT-461. T2D=type 2 diabetes; CKD=chronic kidney disease;
SGLT=sodium-glucose cotransporter; eGFR=estimated glomerular filtration rate; GFR=glomerular filtration rate; UACR=urine albumin:creatinine ratio.
Kohan DE et al. Kidney Int. 2014;85:962-971. Yale JF et al. Diabetes Obes Metab. 2013;15:463-473. Barnett AH et al. Lancet Diabetes Endocrinol.
2014;doi:10.1016/S22138587(13)70208-0. Gilbert RE. Kidney Int. 2013; doi:10.1038/ki.2013.451
The reduction in interglomerular
pressure induced by SGLT2
inhibitors may provide benefits to
patients with CKD
Dapagliflozin demonstrates
potential nephroprotective effects
in combination with renin-
angiotensin system blockade, as
significant reductions in UACR over
50 weeks in patients with T2D and
moderate renal function were
observed
UACR: Urine Albumin Creatinine Ratio
Dapagliflozin in High risk
population

SGLT2i & Diabetic Nephropathy
Image used only for academic purposes SGLT2: Sodium Glucose Co Transporter
Dapa= Dapagliflozin. David Z.I. Cherney et al. Circulation. 2014;129:587-597
CI=confidence interval; UACR=urine albumin: creatinine ratio; DAPA=dapagliflozin; PBO=placebo. Sjöström CD et al.
World Congress of Nephrology. March 13-17, 2015; Cape Town, South Africa. Poster SAT-461. T2D=type 2 diabetes; CKD=chronic kidney disease;
SGLT=sodium-glucose cotransporter; eGFR=estimated glomerular filtration rate; GFR=glomerular filtration rate; UACR=urine albumin:creatinine ratio.
Kohan DE et al. Kidney Int. 2014;85:962-971. Yale JF et al. Diabetes Obes Metab. 2013;15:463-473. Barnett AH et al. Lancet Diabetes Endocrinol. 2014;doi:10.1016/S2213-8587(13)70208-0. Gilbert RE. Kidney Int. 2013; doi:10.1038/ki.2013.451
Possible
Nephroprotection

Patient Populations where I would prefer other OADs
• Type 1 diabetes.
• Patients >75 years
• Patients with eGFR <45mL/min
• Pregnancy and Nursing woman
• Patients with Recurrent UTI / GUI
• Patients with history of volume depletion, dehydration
Views expressed are of the speaker.

Cefalu, et al. ADA 2012; Leiter et al ADA 2012.
• Due to increasing weight gain and hypoglycemic
episodes, Dapagliflozin was added while Insulin dose was
reduced to 55 IU (25% reduction in dose )*. Metformin was
continued.
• Lifestyle intervention program which focused on low-fat
diet and regular exercise was devised and the patient
was counseled to adopt the same.
• Dosage of statins was increased to control lipid
parameters.
• Self-monitoring of diabetes was encouraged to achieve
better results and regular monitoring of blood pressure
was advised.
Management

• Patient’s weight had reduced further 1.5 kg and her lipid
parameters were approaching normal levels.
• HbA1c 7.5%, not reporting episodes of hypoglycemia
At 6 months
Follow-Up
•Weight loss of about 2.5 kg
•HbA1c: 7.9% ; FBS:128 mg/dL; PPBS: 208 mg/dL
•SBP and DBP decreased by 4mmHg and 2mmHg respectively.
•Lipid parameters improved.
•Advised to continue with same medications with no need to increase
Insulin dose
•Lifestyle modifications reinforced
At 3 months:

Take home massage
• SGLT2 inhibitors can be better choice
who has normal renal function (eGFR- >45) along with insulins or OHA in case of
uncontrolled hyperglycemia in type 2 DM

SGLT2 inhibitor -A boon in uncontrolled dm

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