Rationalizing Antidiabetic Therapy --Based on

RSSDI -ESI Guidelines

DR. RAJEEV CHAWLA MD, FRSSDI, FACP(USA) FRCP(UK) FACE(USA)

SENIOR CONSULTANT DIABETOLOGIST
NORTH DELHI DIABETES CENTRE
President RSSDI
President DIPSI
 The Ominous Octet
Islet b-cell

Decreased
Incretin Effect
Impaired Increased
Lipolysis
Insulin Secretion

Islet a-cell

Increased Glucose
Increased
Reabsorption
Glucagon Secretion

Increased Decreased Glucose

HGP Uptake
Neurotransmitter Dysfunction
 Indian Diabetics are Different

Beta-cell
Dysfunction*

Ref: Yagnik C, Nutr. Rev. 59: 1–9.Clinical picture THE LANCET • Vol 363 • January 10, 2004 *: Ref: Diabet Med. 1994 Aug-Sep;11(7):670-7.
 Relevant Factors to the Indian Context
• High prevalence of prediabetes and diabetes
• Onset of T2DM at least a decade earlier that in western countries
• High prevalence of diabetes-related micro and macro vascular complications
• Large rural-urban divide
• Cost of diagnosis, treatment, monitoring and prevention
• Sedentary lifestyles/physical inactivity
• Limited resources
• Poverty and illiteracy
• Psychosocial and cultural factors
• Adherence and compliance to anti-diabetic therapy
 RSSDI-ESI
Clinical Practice Recommendations for the Management of Type 2 Diabetes Mellitus 2020
Summary of Recommendations

Dr. Rajeev Chawla Dr. S. V. Madhu

(President, RSSDI) (President, ESI)
Dr. B. M. Makkar Dr. Sujoy Ghosh
(Secretary, RSSDI) (Secretary, ESI)
Dr. Banshi Saboo Dr. Sanjay Kalra
(President elect, RSSDI) (President elect, ESI)
 Expert Working Groups:
Members of the expert panel group for each section
Diagnosis and Classification
Prevention (Including Screening and Early Detection)
Lifestyle Changes and Medical Nutrition Therapy
Treatment 1: Oral antidiabetic agents
Injectables
Individualizing Therapy
Post prandial hyperglycaemia
Acute Metabolic Complications
Hypoglycaemia
Chronic complications: Neuropathy, nephropathy,
retinopathy
Coordinators SR Aravind, Ganapathi Bantwal
Members: AH Zargar Nihal Thomas, Alok Kanugo
Coordinator: S. V. Madhu, R. M. Anjana
Members: A Ramachandran, Eesh Bhatia, Amitesh Agarwal
Coordinators: Anoop Misra, Naval Vikram,
Members: Parminder Singh, Sambit Das, Vageesh Ayyar
Coordinators: Shashank Joshi, Krishna Seshadri
Members: Vijay Panikar, Sameer Agarwal, V Sringesh
Coordinators: AK Das, Sanjay Agarwal
Members: Ajay Kumar, Sunil Jain, Sujit Jha
Coordinators: Banshi Saboo, AK Singh
Members: Muralidharan, Santosh singh, Rajesh Khadgawat
Coordinators: Hari Kumar, Kaushik Pandit
Members:SK Sharma, Mathew John, Pradip Mukhopadhyay
Coordinators: Jubin Jacob, Anil Bhansali
Members:Sushil Jindal, Kamlakar Tripathi, Narsingh Verma
Coordinators: Anand Moses, Jamal Ahmed
Members:DC Sharma, G Vijaykumar, Dheeraj Kapoor
Coordinators: Rajeev Chawla, Rakesh Sahay
Members:Shalini jaggi, RK Lalwani, Hitesh Punyani
Chronic Complications 2 Coordinators: SK Singh, Vijay Vishwanathan
Stroke, PAD, Diabetic Foot Members:Ashu Rastogi, Ghanshyam Goyal, Ashraf Ganie
Diabetes & CV risk Coordinators: V Mohan, Arvind Gupta
Members:Shaileja Kale, Sudhir Bhandari, RV Jayakumar
Diabetes and Obesity Coordinators: BM Makkar, Neeta Deshpande,
Members: CL Nawal, K A V Sumbramanian, Rucha Mehta
Infection and vaccinations Coordinators: Subhankar Chowdhary, Jayant Panda
Members: Pramod Gandhi, JK Sharma, Vinay Dhandhania
Sexual Dysfunction Coordinators: Samar Banerjee, PK Jabbar
Members: Mithun Bhartiya, Urman Dhruv, Premlata vartakavi
Clinical monitoring Coordinators: Siddhartha Das, AG Unnikrishnan
Members: Rajiv Kovil, Alok Sachan, Girish Varma
Technologies Coordinators: Jothydev, Ambrish Mithal
Members: KM Prasanna kumar, Manoj Chawla, Ameya Joshi
Special Situations - Coordinators: Nikhil Tandon, Padma Menon
Members: Sujoy Ghosh, Nalini Shah, Usha Sriram,
Rajesh Rajput
Fasting and diabetes Coordinators: Sarita Bajaj, Manas Barua
Members: MK Garg, Sachin Chhitawar, Hemant Thacker
Education Coordinators: Vasanth Kumar, Sunil Gupta
Members: Meena Chhabra, Amit Gupta, GD Ramchandani
Psychosocial Issues Coordinators: HB Chandalia, Sanjay Kalra
Members: GR Sridhar, Rishi Shukla, Salam Ranabir
Complementary and Coordinators: PV Rao, Anuj Maheshwari
Alternate Therapies Members: JP Sai, KR Narsimha Setty, Saurabh Srivastava
 Methods
• The current guideline should be considered as ‘derived guideline’ developed the
source IDF 2014 ‘Global Guidelines for Type 2 Diabetes’.
• Analytical re-evaluation of the recommendations proposed by IDF workgroup, was
based on
• Indian evidence published between 1990and 2015
• A review of relevant local factors in Indian context.
• Indian evidence included :
• Indexed literature searches, articles published in International Journal of Diabetes
in Developing countries (IJDDC), RSSDI textbook of Diabetes (3rd edition) ,
Journal of Association of Physicians of India (JAPI) and personal communications
from authors.
• Where Indian evidence was not available Asian evidence was considered if available.
 Methods
• The recommendations of the expert panel groups were reviewed by the steering
committee and were then finalized by the writing group as a draft consensus
document.
• The draft consensus document was sent out for wide consultation :
• National and regional members of all RSSDI chapters
• All key opinion leaders in the country,
• Representatives of other Diabetes and Physician organizations in India
• Interested industry and academic professionals
• To a large section of physicians, diabetologists and endocrinologists in the country.
• The same was also put up on the society website for any suggestions.
• The suggestions/comments provided by them were reviewed by the steering
committee and the draft was accordingly updated, where appropriate.
 RSSDI ESI 2020 Recommendations -
ABCDEFGH Approach for Diabetes Management
RSSDI Diabetic Therapeutic Wheel
From Innermost to Outermost

A → Age = Advancing Age

B → BMI = Increasing BMI

C → CKD = Advancing CKD

D → Duration of Diabetes = Increasing Duration

E → Established CVD = Low CVD risk to Established CVD Risk

F → Finance = Adequate to Limited

G → Glycemic Status = Worsening glycemic control

H → Hypoglycemia = Hypoglycemia concern

Lesser Options available

Wider Options available

RSSDI ESI Diabetic Therapeutic Wheel
From Innermost to Outermost
A → Age = Advancing age
B → BMI = Increasing BMI
C → CKD = Advancing CKD
D → Duration of Diabetes = Increasing duration
E → Established CVD = Low CVD risk to Established CVD Risk
F → Finance = Adequate to Limited
G → Glycemic Status = Worsening glycemic control
H → Hypoglycemia = Hypoglycemia concern
AGI: Alpha-glucosidase inhibitor; DPP4: Dipeptidyl Peptidase-4
(DPP-4) Inhibitors; DPP4-L: Dipeptidyl Peptidase-4 Inhibitors-
Linagliptin;GL: Glinides; GLP: Glucagon-like peptide-1 receptor
agonist; PIO: Pioglitazone; SGLT: Sodium-glucose Cotransporter 2
Inhibitors; SSU: short acting sulphonylureas; Su: Sulphonylurea
LSM - lifestyle modification
Note: Hierarchy of therapy is depicted in clock-wise manner
GLPs must be used based on costs. Any drugs can be used in the
green. For other zones, drugs must be used in the given order.
Individualized Treatment
A –Age (Advancing Age)
B –BMI (Increasing BMI)
C –CKD (Advancing CKD)
D -Duration of Diabetes (Increasing Duration)
 E - Established CVD
(Low CVD risk to Established CVD Risk)
F - Finance (Adequate to Limited)
 G - Glycemic Status
(Worsening Glycemic Control)
H - Hypoglycemia (Hypoglycemia Concern)
Group of Patients Where One Will Require
Avoiding Hypoglycemia Include
How to use the RSSDI Diabetic Therapeutic Wheel ?

• RSSDI therapeutic wheel is designed to be a simple user friendly approach to

decide the appropriate antidiabetic agent to be used in Type 2 Diabetes Mellitus
• When you see a patient in your clinic
• Prescribe lifestyle intervention to all and metformin to most patients as
mentioned in the inner core of the wheel (white and light blue rings)
• Then identify the 2/3 most important concerns / factors (from ABCDEFGH)that
you feel should influence your choice of antidiabetic agent eg. Age / CKD /
Finance etc.
• Identify the best choices available to you from the outer rings of the wheel
(Orange and red)
• Further fine tune your choices if more concerns exist in a given patient and
reach a rational final choice in an ‘individualised approach’
From Innermost to Outermost
A → Age = Advancing age
B → BMI = Increasing BMI
C → CKD = Advancing CKD
D → Duration of Diabetes = Increasing duration
E → Established CVD = Low CVD risk to Established CVD Risk
F → Finance = Adequate to Limited
G → Glycemic Status = Worsening glycemic control
H → Hypoglycemia = Hypoglycemia concern
AGI: Alpha-glucosidase inhibitor; DPP4: Dipeptidyl Peptidase-4
(DPP-4) Inhibitors; DPP4-L: Dipeptidyl Peptidase-4 Inhibitors-
Linagliptin;GL: Glinides; GLP: Glucagon-like peptide-1 receptor
agonist; PIO: Pioglitazone; SGLT: Sodium-glucose Cotransporter 2
Inhibitors; SSU: short acting sulphonylureas; Su: Sulphonylurea
LSM - lifestyle modification
Note: Hierarchy of therapy is depicted in clock-wise manner
GLPs must be used based on costs. Any drugs can be used in the
green. For other zones, drugs must be used in the given order.
 Dr. Rakesh Sahay
Prof. & Head
Department of Endocrinology
Osmania Medical College
Hyderabad
 Case # 1

• 48 years old male businessman with T2DM X 3 years on Metformin

• A1c increasing to 8.4% over past year
• Addl Hx: Further attempts at lifestyle change unsuccesful
• PMH: HTN on Ramipril,
• Declines injectables
• PE: Obese. BMI 32.5. BP 142/84. Acanthosis nigricans
• Data: A1c 8.4%, FPG 187, PPPG 294 Cr 1.1 (eGFR > 60 ) LDL 84
• HDL 38, TG 256, ECG: normal
• Which OAD next?
 Case # 1

• 48 years old male businessman with T2DM X 3 years on Metformin

• A1c increasing to 8.4% over past year
• Addl Hx: Further attempts at lifestyle change unsuccesful
• PMH: HTN on Ramipril,
• Declines injectables
• PE: Obese. BMI 32.5. BP 142/84. Acanthosis nigricans
• Data: A1c 8.4%, FPG 187, PPPG 294 Cr 1.1 (eGFR > 60 ) LDL 84
• HDL 38, TG 256, ECG: normal
• Which OAD next?
From Innermost to Outermost
A → Age = Advancing age
B → BMI = Increasing BMI
C → CKD = Advancing CKD
D → Duration of Diabetes = Increasing duration
E → Established CVD = Low CVD risk to Established CVD Risk
F → Finance = Adequate to Limited
G → Glycemic Status = Worsening glycemic control
H → Hypoglycemia = Hypoglycemia concern
AGI: Alpha-glucosidase inhibitor; DPP4: Dipeptidyl Peptidase-4
(DPP-4) Inhibitors; DPP4-L: Dipeptidyl Peptidase-4 Inhibitors-
Linagliptin;GL: Glinides; GLP: Glucagon-like peptide-1 receptor
agonist; PIO: Pioglitazone; SGLT: Sodium-glucose Cotransporter
2 Inhibitors; SSU: short acting sulphonylureas; Su: Sulphonylurea
LSM - lifestyle modification
Note: Hierarchy of therapy is depicted in clock-wise manner
GLPs must be used based on costs. Any drugs can be used in the
green. For other zones, drugs must be used in the given order.
 Options

• Step up Metformin to 1.5-2.5 gms/ Low dose Pio 15mg

• SGLT-2 Inhibitors
• GLP-1A
 Case #2

• 70 yr M smoker with documented atherosclerosis in carotid and coronary

vasculature
• DM x 12 years; hypoglycemia aware
• A1c 8.6%
• Hx MI, Compensated heart failure
• Stage 2 CKD, microalbuminuria +
• Multiple vascular risk factors
• Which OAD ?
 Case #2

• 70 yr M smoker with documented atherosclerosis in carotid and coronary

vasculature
• DM x 12 years; hypoglycemia aware
• A1c 8.6%
• Hx MI, Compensated heart failure
• Stage 2 CKD, microalbuminuria +
• Multiple vascular risk factors
• Which antidiabetic agent ?
From Innermost to Outermost
A → Age = Advancing age
B → BMI = Increasing BMI
C → CKD = Advancing CKD
D → Duration of Diabetes = Increasing duration
E → Established CVD = Low CVD risk to Established CVD Risk
F → Finance = Adequate to Limited
G → Glycemic Status = Worsening glycemic control
H → Hypoglycemia = Hypoglycemia concern
AGI: Alpha-glucosidase inhibitor; DPP4: Dipeptidyl Peptidase-4
(DPP-4) Inhibitors; DPP4-L: Dipeptidyl Peptidase-4 Inhibitors-
Linagliptin;GL: Glinides; GLP: Glucagon-like peptide-1 receptor
agonist; PIO: Pioglitazone; SGLT: Sodium-glucose Cotransporter 2
Inhibitors; SSU: short acting sulphonylureas; Su: Sulphonylurea
LSM - lifestyle modification
Note: Hierarchy of therapy is depicted in clock-wise manner
GLPs must be used based on costs. Any drugs can be used in the
green. For other zones, drugs must be used in the given order.
 Options

• Continue Metformin
• SGLT-2 Inhibitor if BMI> 25 / GLP-1A
• Sitagliptin ---TECOS
 Case #3

• 60 years old female attendent with T2DM X 7 years on Metformin A1c: 8.4%.
• PMH: hypothyroid. On Atorvastatin, levothyroxine, aspirin
• Questionable adherence. Open to injections
• PE: BMI 26.1, BP 118/76
• Data: A1c 8.4%, FPG 188, Cr 1.7 (eGFR 40), LDL 67. HDL 54, TG 123, ECG:
old IWMI
• Which OAD to add?
 Case #3

• 60 years old female attendent with T2DM X 7 years on Metformin A1c: 8.4%.
• PMH: hypothyroid. On Atorvastatin, levothyroxine, aspirin
• Questionable adherence. Open to injections
• PE: BMI 26.1, BP 118/76
• Data: A1c 8.4%, FPG 188, Cr 1.5 (eGFR 55), LDL 67. HDL 54, TG 123, ECG:
old IWMI
• Which anti diabetic agent to add?
From Innermost to Outermost
A → Age = Advancing age
B → BMI = Increasing BMI
C → CKD = Advancing CKD
D → Duration of Diabetes = Increasing duration
E → Established CVD = Low CVD risk to Established CVD Risk
F → Finance = Adequate to Limited
G → Glycemic Status = Worsening glycemic control
H → Hypoglycemia = Hypoglycemia concern
AGI: Alpha-glucosidase inhibitor; DPP4: Dipeptidyl Peptidase-4
(DPP-4) Inhibitors; DPP4-L: Dipeptidyl Peptidase-4 Inhibitors-
Linagliptin;GL: Glinides; GLP: Glucagon-like peptide-1 receptor
agonist; PIO: Pioglitazone; SGLT: Sodium-glucose Cotransporter 2
Inhibitors; SSU: short acting sulphonylureas; Su: Sulphonylurea
LSM - lifestyle modification
Note: Hierarchy of therapy is depicted in clock-wise manner
GLPs must be used based on costs. Any drugs can be used in the
green. For other zones, drugs must be used in the given order.
 Options

• GLP-1A
• Gliclazide MR
• Sitagliptin 50 mg OD
 Case 4

• 60 M, HT, Business man Diabetic for 7 yrs

• BMI 29.8 % , DYSLIPIDEMIA, LDL 147 , Tgs 276, Chol 226 mg
• Had AMI 3yrs ago , Now compensated , No Angina
• Keen on wt reduction , Open to any therapy
• H/o Hypos twice in last 3 mths
• HBAic 8.2%
 Concerns in this Case

• 60 M, HT, Business man Diabetic for 7 yrs

• BMI 29.8 % , DYSLIPIDEMIA, LDL 147 , Tgs 276, Chol 226 mg
• Had AMI 3yrs ago , Now compensated , No Angina
• Keen on wt reduction , Open to any therapy
• H/o Hypos twice in last 3 mths
• HBAic 8.2%
From Innermost to Outermost
A → Age = Advancing age
B → BMI = Increasing BMI
C → CKD = Advancing CKD
D → Duration of Diabetes = Increasing duration
E → Established CVD = Low CVD risk to Established CVD Risk
F → Finance = Adequate to Limited
G → Glycemic Status = Worsening glycemic control
H → Hypoglycemia = Hypoglycemia concern
AGI: Alpha-glucosidase inhibitor; DPP4: Dipeptidyl Peptidase-4
(DPP-4) Inhibitors; DPP4-L: Dipeptidyl Peptidase-4 Inhibitors-
Linagliptin;GL: Glinides; GLP: Glucagon-like peptide-1 receptor
agonist; PIO: Pioglitazone; SGLT: Sodium-glucose Cotransporter 2
Inhibitors; SSU: short acting sulphonylureas; Su: Sulphonylurea
LSM - lifestyle modification
Note: Hierarchy of therapy is depicted in clock-wise manner
GLPs must be used based on costs. Any drugs can be used in the
green. For other zones, drugs must be used in the given order.
 Options

• Metformin 1-1.5 gm / d
• GLP-1A
• SGLT-2 Inhibitors
 Case 5

• 68 M , Diabetic for 14 yrs , clerk

• Creat 2.3 mg %
• e GFR 32 ml/min
• HBAic 8.9 %
• Tgs 445 mg , LDL 145 mg
• BMI 21.3%
• Anorexic
 Issues

• 68 M , Diabetic for 14 yrs , Low Income group

• Creat 2.3 mg %
• e GFR 32 ml/min
• HBAic 8.9 %
• Tgs 445 mg , LDL 145 mg
• BMI 21.3%
• Anorexic
From Innermost to Outermost
A → Age = Advancing age
B → BMI = Increasing BMI
C → CKD = Advancing CKD
D → Duration of Diabetes = Increasing duration
E → Established CVD = Low CVD risk to Established CVD Risk
F → Finance = Adequate to Limited
G → Glycemic Status = Worsening glycemic control
H → Hypoglycemia = Hypoglycemia concern
AGI: Alpha-glucosidase inhibitor; DPP4: Dipeptidyl Peptidase-4
(DPP-4) Inhibitors; DPP4-L: Dipeptidyl Peptidase-4 Inhibitors-
Linagliptin;GL: Glinides; GLP: Glucagon-like peptide-1 receptor
agonist; PIO: Pioglitazone; SGLT: Sodium-glucose Cotransporter 2
Inhibitors; SSU: short acting sulphonylureas; Su: Sulphonylurea
LSM - lifestyle modification
Note: Hierarchy of therapy is depicted in clock-wise manner
GLPs must be used based on costs. Any drugs can be used in the
green. For other zones, drugs must be used in the given order.
 Best Options

• Stop Metformin
• Insulins ---preferrably Analogues / Pre Mix
 Case 6

• 58 F , Diabetic for 11 yrs

• HBAic 7.9 %
• e GFR 49 ml/min
• Reluctant on insulin thearpy/ Injectables
• Lipids normal
• NPDR , CAD
• BMI 24.8
 Concerns

• 58 F , Diabetic for 11 yrs

• HBAic 7.9 %
• e GFR 49 ml/min
• Reluctant on insulin thearpy/ Injectables
• Lipids normal
• NPDR ,CAD
• BMI 24.8
From Innermost to Outermost
A → Age = Advancing age
B → BMI = Increasing BMI
C → CKD = Advancing CKD
D → Duration of Diabetes = Increasing duration
E → Established CVD = Low CVD risk to Established CVD Risk
F → Finance = Adequate to Limited
G → Glycemic Status = Worsening glycemic control
H → Hypoglycemia = Hypoglycemia concern
AGI: Alpha-glucosidase inhibitor; DPP4: Dipeptidyl Peptidase-4
(DPP-4) Inhibitors; DPP4-L: Dipeptidyl Peptidase-4 Inhibitors-
Linagliptin;GL: Glinides; GLP: Glucagon-like peptide-1 receptor
agonist; PIO: Pioglitazone; SGLT: Sodium-glucose Cotransporter 2
Inhibitors; SSU: short acting sulphonylureas; Su: Sulphonylurea
LSM - lifestyle modification
Note: Hierarchy of therapy is depicted in clock-wise manner
GLPs must be used based on costs. Any drugs can be used in the
green. For other zones, drugs must be used in the given order.
 Options

• Gliptins
• Linagliptin
• Tenaliglitin if pt can’nt afford (caution QT Prolongation ) on high doses
 Case 7

• 46 M , LOW INCOME GROUP Diabetic for 3 yrs

• HBAic 9.1 %
• e GFR 88 ml/min
• Reluctant on insulin thearpy/ Injectables
• Lipids normal
• Early BDR
• BMI 24.8
 Case 7

• 46 M , LOW INCOME GROUP Diabetic for 3 yrs

• HBAic 9.1 %
• e GFR 88 ml/min
• Reluctant on insulin thearpy/ Injectables
• Lipids normal
• Early BDR
• BMI 24.8
 Options

Sus
• Early Insulin-CONVENTIONAL
Thank You