Post on 16-Apr-2017
transcript
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
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Clinical Presentation:
High grade fever X 5 Days
Increasing breathlessness 3 days
Cough with expectoration X 5days
Case Presentation
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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
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General Examination:
• 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
Systemic 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
On Examination
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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 : 11,34,23400LFT : 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
theintensivist@hotmail.com
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
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Limitations with current oral glucose-lowering agentsDo 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. 2001;109:S265–S287.
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 INHIBITORSNewer 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
Dapagliflozin as add-on to insulin (± OADs): 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
Dapagliflozin as add-on to insulin (± OADs): 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 TransporterDapa= Dapagliflozin. David Z.I. Cherney et al. Circulation. 2014;129:587-597CI=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
PossibleNephroprotection
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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
At 6 months
• 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
Follow-Up
At 3 months:
• 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
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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
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