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Final control diabetes keep up to date 10 march 2016

The document discusses managing type 2 diabetes mellitus (T2DM), highlighting pathophysiological mechanisms, pharmacologic treatment options, and the roles of various medications such as metformin, sulfonylureas, and incretin-based therapies. It emphasizes the importance of kidney function in glucose reabsorption and suggests that treatment strategies should be tailored to individual patient needs. Additionally, it explores the risks and benefits associated with different diabetes medications and outlines the evolution of diabetes treatment guidelines over time.

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Control Diabetes: Keep Up-To-Date Alaa Wafa . MD Associate Professor of Internal Medicine Diabetes , Endocrine &Metabolic Disease Unit. Mansoura University
peripheral glucose uptake hepatic glucose production pancreatic insulin secretion pancreatic glucagon secretion gut carbohydrate delivery & absorption incretin effect HYPERGLYCEMIA ? Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011 Multiple, Complex Pathophysiological Abnormalities in T2DM _ _ + renal glucose excretion
Reprinted from Primary Care, 26, Ramlo-Halsted BA, Edelman SV, The natural history of type 2 diabetes. Implications for clinical practice, 771–789, © 1999, with permission from Elsevier. Development and Progression of Type 2 Diabetes and Related Complications* *Conceptual representation. Insulin level Insulin resistance Hepatic glucose production Postprandial glucose Fasting plasma glucose Beta-cell function Progression of Type 2 Diabetes Mellitus Impaired Glucose Tolerance Diabetes Diagnosis Frank Diabetes 4–7 years Development of Macrovascular Complications Development of Microvascular Complications
50 years with NO NEW ADA
Pharmacologic Targets of Current Drugs Used in the Treatment of T2DM 5 -glucosidase inhibitors Delay intestinal carbohydrate absorption Thiazolidinedione Decrease lipolysis in adipose tissue, increase glucose uptake in skeletal muscle and decrease glucose production in liver Sulfonylureas Increase insulin secretion from pancreatic -cells GLP-1 analogs Improve pancreatic islet glucose sensing, slow gastric emptying, improve satiety DDP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1; T2DM=type 2 diabetes mellitus. Adapted from Cheng AY, Fantus IG. CMAJ. 2005; 172: 213–226. Ahrén B, Foley JE. Int J Clin Pract. 2008; 62: 8–14. Glinides Increase insulin secretion from pancreatic -cells DPP-4 inhibitors Prolong GLP-1 action leading to improved pancreatic islet glucose sensing, increase glucose uptake
7 ß-cell: SUs work by closing K+ATP channels  Bind to ATP-dependent potassium (K+) channel (KATP) on the surface of cells, such as the pancreatic beta cell  Stimulate the release of insulin from functioning pancreatic beta-cells regardless of meals and prevailing glucose levels (glucose-independent)  No effect on hepatic glucose overproduction
SULFONYLUREAS Main Advantages • Fast significant effect • Low drug cost • Long experience Main Disadvantages • Hypoglycemia • Weight gain • Loss of effectiveness by time (hasten decline of B cell function)
9 UKPDS 34. Lancet 1998:352:854–865. n=at baseline; Changeinweight(kg) Years from randomisation *diet initially then sulphonylureas, insulin and/or metformin if FPG >15 mmol/l 0 1 5 0 3 6 9 12 8 7 6 4 3 2 Insulin (n=409) Glibenclamide (n=277) Metformin (n=342) Conventional treatment (n=411)* Insulin SU Conv. Met SU and weight gain (UPKPS 34)
Drug Interactions with sulphonylurea Increased Hypoglycemia : • Anticoagulants • Salicylates • Sulfonamides • MAO Inhibitors • Tricyclic antidepressants • Azole antifungals Decreased Action : • Beta Blockers, Diuretics, • Ca channel Blockers • Corticosteroids, • Estrogens, Thyroid Hormones • Sympathomimetics, • Phenothiazines • Isoniazid, Phenytoin, • Nicotinic Acid
Metformin history • Metformin was discovered in 1922.1 Study in humans began in 1950s by French physician Jean Sterne.1 • It was introduced in France in 1957 and the United States in 1995 2 • It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.3 • Metformin is believed to be the most widely used medication for diabetes which is take by mouth1 1. John Wiley & Sons. pp. 47–49. ISBN 9783527632121. 2. St. Louis, Mo.: Mosby/Elsevier. p. 217. ISBN 9780323029643. 3. World Health Organization. October 2013. Retrieved 22 April 2014
Metformin 1. Reduction of excessive Hepatic Glucose Output 2. Stimulation of insulin-mediated muscle glucose uptake -glycogen synthesis is increased 3. Inhibition of lipolysis and of FFA availability Metabolic actions
Metformin 1. Increased insulin binding 2. Stimulation of insulin receptor tyrosine kinase activity 3. Enhanced glucose transport (GLUT 4. Increased glycogen synthase 5. Doesn't cause hypoglycemia Cellular actions
Metformin 1. Favorable lipid effects 2. Weight loss 3. Increased fibrinolytic activity 4. Decreased platelet aggregability 5. Favorable effect on hypertension Additional actions Recently proved that , Fasting total GLP-1 was significantly increased by metformin and After oral glucose, metformin increased significantly total GLP-1.
UKPDS: Risk reduction with metformin in overweight patients N = 4075 with type 2 diabetes UKPDS Group. Lancet. 1998;352:854-65. Favors metformin or intensive Favors conventional All-cause mortality Metformin Intensive Myocardial infarction Metformin Intensive Stroke Metformin Intensive 0.021 0.021 0.021 Aggregate endpoints P* 0.1 1 10 *metformin vs intensive therapy Relative risk reduction (95% CI)
Metformin- side effects 1. Nausea, vomiting, distension 2. Loss of appetite, diarrhoea 3. Skin rashes, urticaria 4. Increase in liver enzymes 5. Rare – Lactic acidosis.
• Hypersensitivity to metformin • Advanced liver disease • CHF ? • Metabolic acidosis • Renal disease (serum creatinine >1.5 mg/dL in males or >1.4mg/dL in females) ? UK:  dose @GFR <45 & stop @GFR <30 • Abnormal creatinine clearance resulting from shock, septicemia, or myocardial infarction • Radiologic contrast study for 48 hr after • Lactation ? Metformin - contraindications
Thiazolidinediones (TZD’s) : make cells more sensitive to insulin (esp. fatty cells) Pioglitazone • Binds to and activates the gamma isoform of the peroxisome proliferator- activated receptor (PPARγ). • PPARγ is a member of the steroid hormone nuclear receptor superfamily, and is found in adipose tissue, • cardiac and skeletal muscle, liver and placenta PPAR - γ • Upon activation of this nuclear receptor by a ligand such as a TZD, PPARγ–ligand complex binds to a specific region of DNA and thereby regulates the transcription of many genes involved in glucose and fatty acid metabolism. S NH O O ON 5-{4-[2-(5-Ethyl-pyridin-2-yl)-ethoxy]-benzyl}-thiazolidine-2,4-dione PPAR γ: peroxisome proliferator-activated receptor
TZDs Main Advantages • Sustained glycemic control • Low risk of hypoglycemia • FDC with metformin & SUs Main Disadvantages • Weight gain • Peripheral edema • Increased risk of CHF • Increased risk of fractures • Drug cost
Meglitinides : Short acting insulin secretagogues - REPAGLINIDE - NATEGLINIDE O OHO NH N O 2-Ethoxy-4-{[3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl]-methyl}-benzoic acid O OH NH O 2-[(4-Isopropyl-cyclohexanecarbonyl)-amino]-3-phenyl-propionic acid
Glinides (Prandial Glucose Regulators) MOA: •Same as SUs but • Short acting • Glucose dependant • Restore first phase insulin response • Reduce post meal glucose level Characteristics: • Reduce postprandial blood glucose • Weight gain • Mild hypoglycemia • Lacking long term efficacy/ safety data • Inconvenient dosing • Drug cost
Αlpha – glycosidase inhibitors : Block enzymes that help digest starches  slowing the rise in B.G.L. - Acarbose - Miglitol N OO O O O H H H H H 1-(2-Hydroxy-ethyl)-2-hydroxymethyl- piperidine-3,4,5-triol
Alpha Glucosidase Inhibitors Advantage • Weight neutral • Low risk of hypoglycemia • Serious side effects are rare Disadvantages • Modest glucose lowering efficacy • GIT side effects (abdominal pain, diarrhea, bloating& flatulence) • Inconvenient dosing
What’s new in Diabetes management in the 21st century
Incretins • Gut-derived hormones, secreted in response to nutrient ingestion, that potentiate insulin secretion from islet  cells in a glucose-dependent fashion, and lower glucagon secretion from islet  cells • Two predominant incretins: – Glucagon-like peptide–1 (GLP-1) – Glucose-dependent insulinotropic peptide (GIP) (also known as gastric inhibitory peptide) • Incretin effect is impaired in type 2 diabetes – Known as GLP-1 deficiency
The Incretin Effect: Insulin Secretion Is Greater in Response to Oral vs IV Glucose 0 50 100 150 200 -30 0 30 60 90 120 150 180 210 Time (min) Glucose(mg/dL) Insulin(pmol/L) 0 100 200 300 400 -30 0 30 60 90 120 150 180 210 Time (min) Oral IV Nauck M et al. J Clin Endocrinol Metab. 1986;63:492-498. Effect diminished in diabetes
DPP4-Is Enhances Active Incretin Levels Through Inhibition of DPP-41–4 By increasing and prolonging active incretin levels, DPP4-Is increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. Release of active incretins GLP-1 and GIPa  Blood glucose in fasting and postprandial states Ingestion of food  Glucagon from alpha cells (GLP-1)  Hepatic glucose production GI tract DPP-4 enzyme Inactive GLP-1 X(DPP-4 inhibitor)  Insulin from beta cells (GLP-1 and GIP) Glucose-dependent Glucose-dependent Pancreas Inactive GIP Beta cells Alpha cells  Peripheral glucose uptake DPP-4=dipeptidyl peptidase 4; GI=gastrointestinal; GIP=glucose-dependent insulinotropic peptide; GLP-1=glucagon-like peptide-1. aIncretin hormones GLP-1 and GIP are released by the intestine throughout the day, and their levels increase in response to a meal. 1. Kieffer TJ et al. Endocr Rev. 1999;20(6):876–913. 2. Ahrén B. Curr Diab Rep. 2003;3(5):365–372. 3. Drucker DJ. Diabetes Care. 2003;26(10):2929–2940, 4. Holst JJ. Diabetes Metab Res Rev. 2002;18(6):430–441. Mode of Action of DPP4-Is
DPP-4 Inhibitors MOA Advantage • Incretin Enhancers • Inhibits the dipeptidyl-peptidase 4 enzyme and thus prevent rapid degradation of GLP-1 and GIP and improves glucose homeostasis • Glucose dependent • Physiologic MOA • Weight neutral • Low risk of hypoglycemia • FDCs with Metformin Members: Sitagliptin, Saxagliptin, Vildagliptin, Alogliptin & Linagliptin
GLP-1 Agonists MOA Advantage Diadvantage Incretin mimetic Mimics the action of GLP-1. • Raise exogenous GLP-1 plasma concentrations into the pharmacologic range • Weight loss • Low risk of hypoglycemia • Serious side effects are rare • GIT side effects (nausea, vomiting & diarrhoea) • SC injection • Drug cost Members: Exenatide & Liraglutide Dosing: SC injection once or twice daily
Functions of the kidney 35 Filtration and reabsorption Acid/base balance Electrolyte Balance Excretion of toxic substances Hormone production: • Calcitrol (healthy bones) • Renin (BP regulation) • Erythropoieitin (red blood cell production) Glucose reabsorption and gluconeogenesis
The kidneys’ contribution to glucose homeostasis • Kidneys contribute to glucose homeostasis in many ways including: producing, filtering, reabsorbing and excreting glucose • The kidneys produce approximately 20-25%1,2 of the total endogenous glucose production • In a healthy individual* virtually all of the filtered glucose is actively reabsorbed into the blood by the sodium glucose co-transporters 2 and 1 (SGLT2 and SGLT1); virtually none is excreted in the urine2,3 36 *Normal physiological blood glucose range <6.5mmol/L before meals and <7.8mmol/L after meals References: 1. Gerich JE. Physiology of glucose homeostasis. Diabetes Obes Metab. 2000;2:345-50. 2. Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet Med. 2010 Feb;27(2):136-42. 3. Mitrakou A. Kidney: its impact on glucose homeostasis and hormonal regulation. Diabetes Res Clin Pract. 2011 Aug;93 Suppl 1:S66-72
The role of the kidney in glucose reabsorption • There are two main sodium- glucose cotransporters: SGLT2 and SGLT11 • SGLT2 is mainly found in the proximal tubules of the kidneys1 • SGLT2 is responsible for reabsorbing approximately 90% of the glucose reabsorbed by the kidney2 • The remaining glucose is reabsorbed by SGLT1 further along the proximal tubule1 • The reabsorbed glucose is then returned to the blood2 37 Adapted from Nair S, Wilding JP. J Clin Endocrinol Metab. 2010;95:34-42. Reference: 1. Nair S, Wilding JP. J Clin Endocrinol Metab. 2010;95:34-42. 2. DeFronzo RA, et al. Diabetes Obes Metab. 2012;14:5-14.
Glucose Transport in Tubular Epithelial Cells G Glucose Na+ Sodium K Potassium BloodLumen S1 Proximal Tubule G Na+ K GLUT2 ATPase SGLT2 High Capacity Low Affinity BloodLumen S3 Proximal Tubule G 2Na+ 2K GLUT1 ATPase SGLT1 Low Capacity High Affinity Adapted from Bakris GL et al. Kidney Int 2009;75:1272-7 Marsenic O. Am J Kidney Dis. 2009;53:875-83
Glucose Reabsorption in a Nondiabetic Person (Plasma Glucose <10 mmol/L ) Glomerulus Proximal Convoluted Tubule Glucose reabsorption into tissue Early Distal Glucose SGLT1SGLT2 Urine Adapted with permission from Rothenberg PL et al. SGLT = sodium-glucose linked co-transporter. Rothenberg PL et al. Poster presented at EASD 2010; Stockholm, Sweden
The role of the kidney in glucose reabsorption 41 ~180L filtered per day by the kidney1 References: 1. DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab. 2012 Jan;14(1):5-14. 2. Clifford J. Bailey. Medscape Education Diabetes & Endocrinology. The Role of the Kidney in Glucose Control.. CME Released: 02/26/2013 ; Valid for credit through 02/26/2014. A normal kidney A kidney in a patient with type 2 diabetes Average blood glucose of ~100mg/dL2 Average blood glucose of ~150mg/dL2 ~180g of glucose filtered per day2 No increase in SGLT2 cotransporters2 ~250g of glucose filtered per day2  glucose reabsorption and  elimination of glucose in the urine2 Hyperglycaemia Increase in SGLT2 cotransporters2
Glucose Reabsorption in a Person With T2DM (Plasma Glucose >10 and <13.3 mmol/L) Glomerulus Proximal Convoluted Tubule Increased glucose reabsorption into tissue compared to normal Early Distal Urine Adapted with permission from Rothenberg PL et al. SGLT = sodium-glucose linked co-transporter. Rothenberg PL et al. Poster presented at EASD 2010; Stockholm, Sweden Glucose SGLT1SGLT2
Effects of SGLT2 Inhibitors Inhibition of renal tubular Na+- glucose co-transporter reversal of hyperglycemia reversal of “glucotoxicity” Insulin sensitivity in muscle Insulin sensitivity in liver Gluconeogenesis Improved beta cell function DeFronzo RA, et al. Diabetes Obes Metab. 2012;14(1):5-14.
Trends in Treatment of T2DM from 1997 to 2012 in USA Sulfonylureas Insulin GLP-1 agonist
We have many different guidelines
What Guidelines Say?
Treating patients should be to targets with consideration of patients individualization FPG <110 mg/dl FPG <130 mg/dl HbA1c <7.0% HbA1c <7.0% ADA1,2/ EASD2 IDF3 PPG < 160 mg/dl PPG <180 mg/dl 1. American Diabetes Association Diabetes Care 2009;32 (Suppl 1):S1-S97 2. ADA/EASD Consensus guideline. Diabetes Care 2009;32(1): 193-203 3. IDF Treatment Algorithm for People with Type 2 Diabetes. 2011
Smoking Lifestyle Control blood pressure Education Statin Metformin Aspirin Control blood glucose Individualised care of patients: based on evidence for each intervention Type 2 diabetes management is multifactorial
peripheral glucose uptake hepatic glucose production pancreatic insulin secretion pancreatic glucagon secretion gut carbohydrate delivery & absorption incretin effect HYPERGLYCEMIA ? Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011 Multiple, Complex Pathophysiological Abnormalities in T2DM _ _ + renal glucose excretion
peripheral glucose uptake hepatic glucose production pancreatic insulin secretion pancreatic glucagon secretion gut carbohydrate delivery & absorption incretin effect HYPERGLYCEMIA ? Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011 Multiple, Complex Pathophysiological Abnormalities in T2DM _ _ + renal glucose excretion DA agonists T Z D sMetformin S U sGlinides DPP-4 inhibitors GLP-1R agonists A G I s Amylin mimetics Insulin Bile acid sequestrants
What’s missing 5 principles in selecting Antihyperglycemic interventions 1. Efficacy 2. Hypoglycemia 3. Weight 4. Side effects 5. Cost
Standards of Medical Care in Diabetes — 2016
Healthy eating, weight control, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-ior or or GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + Figure 2. Anti-hyperglycemic therapy in T2DM: General recommendations Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-ior or or GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + Figure 2. Anti-hyperglycemic therapy in T2DM: General recommendations Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-ior or or GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + Figure 2. Anti-hyperglycemic therapy in T2DM: General recommendations Diabetes Care 2016;38:140-149; Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-ior or or GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-ior or or GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442 HbA1c ≥9% Metformin intolerance or contraindication Uncontrolled hyperglycemia (catabolic features, BG ≥300-350 mg/dl, HbA1c ≥10-12%)
Healthy eating, weight control, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-i GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin or or or Insulin (basal) + Figure 2A. Anti-hyperglycemic therapy in T2DM: Avoidance of hypoglycemia Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-i GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + or or or Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442 Figure 2B. Anti-hyperglycemic therapy in T2DM: Avoidance of weight gain
1-Aspirin therapy for women aged 50 and older(changed from women ›60 previously) 2-antiplatlet use in patients younger than 50 with multiple risk factor 3- addition of Ezetimibe to moderate-intensity statin therapy in patient with diabetes based on Recent IMPROVED-IT trial. 4-- some linguistic shift as ASCVD is more specific than CVD, And Diabetic Kidney Disease DKD instead of nephropathy. 5-tailoring treatment for vulnerable populations with diabetes ,such as HIV infection, Mental illness Food insecurity. What is new in ADA 2016?
● Diabetes treatment must be individualized, patient-centered, and culturally appropriate. ● In Asian Americans, consider DM testing in adults of any age with 1 risk factor and a BMI ≥23. ● To decrease disparities, all providers and groups are encouraged to use the National Quality Forum’s National Voluntary Consensus Standards for Ambulatory Care— Measuring Healthcare Disparities Tailoring Treatment American Diabetes Association Standards of Medical Care in Diabetes. Strategies for improving diabetes care. Diabetes Care 2016; 39 (Suppl. 1): S6-S12
● Lack of health insurance ● Food insecurity (FI) o Carefully evaluate hyperglycemia and hypoglycemia and propose solutions A o Recognize that homelessness and poor literacy often occur with food insecurity; appropriate resources should be made available for patients with diabetes. A Health Disparities American Diabetes Association Standards of Medical Care in Diabetes. Strategies for improving diabetes care. Diabetes Care 2016; 39 (Suppl. 1): S6-S12
1. Intensive glucose control is not advised for the improvement of poor cognitive function in hyperglycemic individuals with T2DM. B 2. In individuals with poor cognitive function or severe hypoglycemia, glycemic therapy should be tailored to avoid significant hypoglycemia. C Cognitive Dysfunction American Diabetes Association Standards of Medical Care in Diabetes. Strategies for improving diabetes care. Diabetes Care 2016; 39 (Suppl. 1): S6-S12
3. In individuals with diabetes at high CVD risk, the cardiovascular benefits of statin therapy outweigh the risk of cognitive dysfunction. A 4. If a second-generation antipsychotic medication is prescribed, changes in weight, glycemic control, and cholesterol levels, should be carefully monitored and the treatment regimen reassessed. C Cognitive Dysfunction (2) American Diabetes Association Standards of Medical Care in Diabetes. Strategies for improving diabetes care. Diabetes Care 2016; 39 (Suppl. 1): S6-S12
● Screen patients with HIV for diabetes and prediabetes before starting antiretroviral (ARV) therapy, and 3 months after starting or changing it. E ● If initial screening results are normal, check fasting glucose annually. E ● If prediabetes is detected, continue to measure levels every 3-6 months to monitor for progression to diabetes. E Human Immunodeficiency Virus (HIV) American Diabetes Association Standards of Medical Care in Diabetes. Strategies for improving diabetes care. Diabetes Care 2016; 39 (Suppl. 1): S6-S12
New section of Obesity ,covering life style modofication,pharmacological management & bariatric surgery has been added. Cont. What is new in ADA 2016?
● Guidelines support gastric banding, gastrectomy, and bypass as effective treatments for overweight T2DM patients. ● In 72% of patients, bariatric surgery helped achieve near- or complete normalization of glycemia 2 yrs post- surgery. ● In one meta-analysis, gastric banding resulted in less weight loss than gastrectomy or Roux-en-Y. Bariatric Surgery American Diabetes Association Standards of Medical Care in Diabetes. Obesity management for the treatment of type 2 diabetes. Diabetes Care 2016; 39 (Suppl. 1): S47-S51
● Bariatric surgery may be considered for adults with BMI >35 and T2DM, especially if diabetes or associated comorbidities are difficult to control with lifestyle & medications. B ● Patients with T2DM who have undergone bariatric surgery need lifelong lifestyle support and annual medical monitoring, at a minimum. B Recommendations: Bariatric Surgery American Diabetes Association Standards of Medical Care in Diabetes. Obesity management for the treatment of type 2 diabetes. Diabetes Care 2016; 39 (Suppl. 1): S47-S51
● Although small trials have shown glycemic benefit of bariatric surgery in patients with T2DM and BMI 30–35, there is currently insufficient evidence to generally recommend surgery in patients with BMI ≤35. E Recommendations: Bariatric Surgery American Diabetes Association Standards of Medical Care in Diabetes. Obesity management for the treatment of type 2 diabetes. Diabetes Care 2016; 39 (Suppl. 1): S47-S51
● Costly ● Some associated risks ● Outcomes vary ● Patients undergoing bariatric surgery may be at higher risk for substance abuse including drug and alcohol use and cigarette smoking. Disadvantages of bariatric surgery American Diabetes Association Standards of Medical Care in Diabetes. Obesity management for the treatment of type 2 diabetes. Diabetes Care 2016; 39 (Suppl. 1): S47-S51
Despite treatment advances, mean HbA1C in type 2 diabetes is elevated in most countries Canada 7.36–8.7%11 Latin America 7.6%1 US 7.2%7 China 9.5%11 India 8.7–9.6%9,11 Japan 7.05–9.6%11 Korea 7.9–8.7%4 Russia 9.6%11 Spain 9.2%8 Sweden 8.7%3 Turkey 10.6%3 UK 8.510–9.8%2 Germany 8.42–9.2%8 Greece 8.911–9.7%3,8 Italy 8.4%11 Poland 9.0%11 Portugal 9.7%3 Romania 9.9%3 1. Lopez Stewart et al. Rev Panam Salud Publica 2007;22:12–20; 2. Kostev & Rathmann Primary Care Diabetes 2013;7:229–33; 3. Oguz et al. Curr Med Res Opin 2013;29:911–20; 4. Ko et al. Diab Med 2007;24:55–62; 5. Arai et al. Diab Res Clin Prac 2009;83:397–401; 6. Harris et al. Diabetes Res Clin Pract 2005;70:90–7; 7. Hoerger et.al. Diabetes Care 2008;31:81–6; 8. Liebl et al. Diab Ther 2012;3:e1–10; 9. Shah et al. Adv Ther 2009;26:325–35; 10. Blak et al. Diab Med 2012;29:e13–20; 11. Valensi et al. Int J Clin Pract 2008;62:1809–19
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Final control diabetes keep up to date 10 march 2016

  • 1.
    Control Diabetes: KeepUp-To-Date Alaa Wafa . MD Associate Professor of Internal Medicine Diabetes , Endocrine &Metabolic Disease Unit. Mansoura University
  • 2.
    peripheral glucose uptake hepatic glucose production pancreatic insulin secretion pancreatic glucagon secretion gut carbohydrate delivery & absorption incretin effect HYPERGLYCEMIA ? Adapted from:Inzucchi SE, Sherwin RS in: Cecil Medicine 2011 Multiple, Complex Pathophysiological Abnormalities in T2DM _ _ + renal glucose excretion
  • 3.
    Reprinted from PrimaryCare, 26, Ramlo-Halsted BA, Edelman SV, The natural history of type 2 diabetes. Implications for clinical practice, 771–789, © 1999, with permission from Elsevier. Development and Progression of Type 2 Diabetes and Related Complications* *Conceptual representation. Insulin level Insulin resistance Hepatic glucose production Postprandial glucose Fasting plasma glucose Beta-cell function Progression of Type 2 Diabetes Mellitus Impaired Glucose Tolerance Diabetes Diagnosis Frank Diabetes 4–7 years Development of Macrovascular Complications Development of Microvascular Complications
  • 4.
    50 years withNO NEW ADA
  • 5.
    Pharmacologic Targets ofCurrent Drugs Used in the Treatment of T2DM 5 -glucosidase inhibitors Delay intestinal carbohydrate absorption Thiazolidinedione Decrease lipolysis in adipose tissue, increase glucose uptake in skeletal muscle and decrease glucose production in liver Sulfonylureas Increase insulin secretion from pancreatic -cells GLP-1 analogs Improve pancreatic islet glucose sensing, slow gastric emptying, improve satiety DDP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1; T2DM=type 2 diabetes mellitus. Adapted from Cheng AY, Fantus IG. CMAJ. 2005; 172: 213–226. Ahrén B, Foley JE. Int J Clin Pract. 2008; 62: 8–14. Glinides Increase insulin secretion from pancreatic -cells DPP-4 inhibitors Prolong GLP-1 action leading to improved pancreatic islet glucose sensing, increase glucose uptake
  • 7.
    7 ß-cell: SUs work byclosing K+ATP channels  Bind to ATP-dependent potassium (K+) channel (KATP) on the surface of cells, such as the pancreatic beta cell  Stimulate the release of insulin from functioning pancreatic beta-cells regardless of meals and prevailing glucose levels (glucose-independent)  No effect on hepatic glucose overproduction
  • 8.
    SULFONYLUREAS Main Advantages • Fastsignificant effect • Low drug cost • Long experience Main Disadvantages • Hypoglycemia • Weight gain • Loss of effectiveness by time (hasten decline of B cell function)
  • 9.
    9 UKPDS 34. Lancet1998:352:854–865. n=at baseline; Changeinweight(kg) Years from randomisation *diet initially then sulphonylureas, insulin and/or metformin if FPG >15 mmol/l 0 1 5 0 3 6 9 12 8 7 6 4 3 2 Insulin (n=409) Glibenclamide (n=277) Metformin (n=342) Conventional treatment (n=411)* Insulin SU Conv. Met SU and weight gain (UPKPS 34)
  • 10.
    Drug Interactions with sulphonylurea IncreasedHypoglycemia : • Anticoagulants • Salicylates • Sulfonamides • MAO Inhibitors • Tricyclic antidepressants • Azole antifungals Decreased Action : • Beta Blockers, Diuretics, • Ca channel Blockers • Corticosteroids, • Estrogens, Thyroid Hormones • Sympathomimetics, • Phenothiazines • Isoniazid, Phenytoin, • Nicotinic Acid
  • 12.
    Metformin history • Metformin wasdiscovered in 1922.1 Study in humans began in 1950s by French physician Jean Sterne.1 • It was introduced in France in 1957 and the United States in 1995 2 • It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.3 • Metformin is believed to be the most widely used medication for diabetes which is take by mouth1 1. John Wiley & Sons. pp. 47–49. ISBN 9783527632121. 2. St. Louis, Mo.: Mosby/Elsevier. p. 217. ISBN 9780323029643. 3. World Health Organization. October 2013. Retrieved 22 April 2014
  • 13.
    Metformin 1. Reduction ofexcessive Hepatic Glucose Output 2. Stimulation of insulin-mediated muscle glucose uptake -glycogen synthesis is increased 3. Inhibition of lipolysis and of FFA availability Metabolic actions
  • 14.
    Metformin 1. Increased insulinbinding 2. Stimulation of insulin receptor tyrosine kinase activity 3. Enhanced glucose transport (GLUT 4. Increased glycogen synthase 5. Doesn't cause hypoglycemia Cellular actions
  • 15.
    Metformin 1. Favorable lipideffects 2. Weight loss 3. Increased fibrinolytic activity 4. Decreased platelet aggregability 5. Favorable effect on hypertension Additional actions Recently proved that , Fasting total GLP-1 was significantly increased by metformin and After oral glucose, metformin increased significantly total GLP-1.
  • 16.
    UKPDS: Risk reductionwith metformin in overweight patients N = 4075 with type 2 diabetes UKPDS Group. Lancet. 1998;352:854-65. Favors metformin or intensive Favors conventional All-cause mortality Metformin Intensive Myocardial infarction Metformin Intensive Stroke Metformin Intensive 0.021 0.021 0.021 Aggregate endpoints P* 0.1 1 10 *metformin vs intensive therapy Relative risk reduction (95% CI)
  • 17.
    Metformin- side effects 1.Nausea, vomiting, distension 2. Loss of appetite, diarrhoea 3. Skin rashes, urticaria 4. Increase in liver enzymes 5. Rare – Lactic acidosis.
  • 18.
    • Hypersensitivity tometformin • Advanced liver disease • CHF ? • Metabolic acidosis • Renal disease (serum creatinine >1.5 mg/dL in males or >1.4mg/dL in females) ? UK:  dose @GFR <45 & stop @GFR <30 • Abnormal creatinine clearance resulting from shock, septicemia, or myocardial infarction • Radiologic contrast study for 48 hr after • Lactation ? Metformin - contraindications
  • 20.
    Thiazolidinediones (TZD’s) :make cells more sensitive to insulin (esp. fatty cells) Pioglitazone • Binds to and activates the gamma isoform of the peroxisome proliferator- activated receptor (PPARγ). • PPARγ is a member of the steroid hormone nuclear receptor superfamily, and is found in adipose tissue, • cardiac and skeletal muscle, liver and placenta PPAR - γ • Upon activation of this nuclear receptor by a ligand such as a TZD, PPARγ–ligand complex binds to a specific region of DNA and thereby regulates the transcription of many genes involved in glucose and fatty acid metabolism. S NH O O ON 5-{4-[2-(5-Ethyl-pyridin-2-yl)-ethoxy]-benzyl}-thiazolidine-2,4-dione PPAR γ: peroxisome proliferator-activated receptor
  • 21.
    TZDs Main Advantages • Sustainedglycemic control • Low risk of hypoglycemia • FDC with metformin & SUs Main Disadvantages • Weight gain • Peripheral edema • Increased risk of CHF • Increased risk of fractures • Drug cost
  • 23.
    Meglitinides : Shortacting insulin secretagogues - REPAGLINIDE - NATEGLINIDE O OHO NH N O 2-Ethoxy-4-{[3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl]-methyl}-benzoic acid O OH NH O 2-[(4-Isopropyl-cyclohexanecarbonyl)-amino]-3-phenyl-propionic acid
  • 24.
    Glinides (Prandial GlucoseRegulators) MOA: •Same as SUs but • Short acting • Glucose dependant • Restore first phase insulin response • Reduce post meal glucose level Characteristics: • Reduce postprandial blood glucose • Weight gain • Mild hypoglycemia • Lacking long term efficacy/ safety data • Inconvenient dosing • Drug cost
  • 26.
    Αlpha – glycosidaseinhibitors : Block enzymes that help digest starches  slowing the rise in B.G.L. - Acarbose - Miglitol N OO O O O H H H H H 1-(2-Hydroxy-ethyl)-2-hydroxymethyl- piperidine-3,4,5-triol
  • 27.
    Alpha Glucosidase Inhibitors Advantage •Weight neutral • Low risk of hypoglycemia • Serious side effects are rare Disadvantages • Modest glucose lowering efficacy • GIT side effects (abdominal pain, diarrhea, bloating& flatulence) • Inconvenient dosing
  • 28.
    What’s new inDiabetes management in the 21st century
  • 29.
    Incretins • Gut-derived hormones,secreted in response to nutrient ingestion, that potentiate insulin secretion from islet  cells in a glucose-dependent fashion, and lower glucagon secretion from islet  cells • Two predominant incretins: – Glucagon-like peptide–1 (GLP-1) – Glucose-dependent insulinotropic peptide (GIP) (also known as gastric inhibitory peptide) • Incretin effect is impaired in type 2 diabetes – Known as GLP-1 deficiency
  • 30.
    The Incretin Effect:Insulin Secretion Is Greater in Response to Oral vs IV Glucose 0 50 100 150 200 -30 0 30 60 90 120 150 180 210 Time (min) Glucose(mg/dL) Insulin(pmol/L) 0 100 200 300 400 -30 0 30 60 90 120 150 180 210 Time (min) Oral IV Nauck M et al. J Clin Endocrinol Metab. 1986;63:492-498. Effect diminished in diabetes
  • 31.
    DPP4-Is Enhances ActiveIncretin Levels Through Inhibition of DPP-41–4 By increasing and prolonging active incretin levels, DPP4-Is increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. Release of active incretins GLP-1 and GIPa  Blood glucose in fasting and postprandial states Ingestion of food  Glucagon from alpha cells (GLP-1)  Hepatic glucose production GI tract DPP-4 enzyme Inactive GLP-1 X(DPP-4 inhibitor)  Insulin from beta cells (GLP-1 and GIP) Glucose-dependent Glucose-dependent Pancreas Inactive GIP Beta cells Alpha cells  Peripheral glucose uptake DPP-4=dipeptidyl peptidase 4; GI=gastrointestinal; GIP=glucose-dependent insulinotropic peptide; GLP-1=glucagon-like peptide-1. aIncretin hormones GLP-1 and GIP are released by the intestine throughout the day, and their levels increase in response to a meal. 1. Kieffer TJ et al. Endocr Rev. 1999;20(6):876–913. 2. Ahrén B. Curr Diab Rep. 2003;3(5):365–372. 3. Drucker DJ. Diabetes Care. 2003;26(10):2929–2940, 4. Holst JJ. Diabetes Metab Res Rev. 2002;18(6):430–441. Mode of Action of DPP4-Is
  • 32.
    DPP-4 Inhibitors MOA Advantage •Incretin Enhancers • Inhibits the dipeptidyl-peptidase 4 enzyme and thus prevent rapid degradation of GLP-1 and GIP and improves glucose homeostasis • Glucose dependent • Physiologic MOA • Weight neutral • Low risk of hypoglycemia • FDCs with Metformin Members: Sitagliptin, Saxagliptin, Vildagliptin, Alogliptin & Linagliptin
  • 33.
    GLP-1 Agonists MOA AdvantageDiadvantage Incretin mimetic Mimics the action of GLP-1. • Raise exogenous GLP-1 plasma concentrations into the pharmacologic range • Weight loss • Low risk of hypoglycemia • Serious side effects are rare • GIT side effects (nausea, vomiting & diarrhoea) • SC injection • Drug cost Members: Exenatide & Liraglutide Dosing: SC injection once or twice daily
  • 35.
    Functions of thekidney 35 Filtration and reabsorption Acid/base balance Electrolyte Balance Excretion of toxic substances Hormone production: • Calcitrol (healthy bones) • Renin (BP regulation) • Erythropoieitin (red blood cell production) Glucose reabsorption and gluconeogenesis
  • 36.
    The kidneys’ contributionto glucose homeostasis • Kidneys contribute to glucose homeostasis in many ways including: producing, filtering, reabsorbing and excreting glucose • The kidneys produce approximately 20-25%1,2 of the total endogenous glucose production • In a healthy individual* virtually all of the filtered glucose is actively reabsorbed into the blood by the sodium glucose co-transporters 2 and 1 (SGLT2 and SGLT1); virtually none is excreted in the urine2,3 36 *Normal physiological blood glucose range <6.5mmol/L before meals and <7.8mmol/L after meals References: 1. Gerich JE. Physiology of glucose homeostasis. Diabetes Obes Metab. 2000;2:345-50. 2. Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet Med. 2010 Feb;27(2):136-42. 3. Mitrakou A. Kidney: its impact on glucose homeostasis and hormonal regulation. Diabetes Res Clin Pract. 2011 Aug;93 Suppl 1:S66-72
  • 37.
    The role ofthe kidney in glucose reabsorption • There are two main sodium- glucose cotransporters: SGLT2 and SGLT11 • SGLT2 is mainly found in the proximal tubules of the kidneys1 • SGLT2 is responsible for reabsorbing approximately 90% of the glucose reabsorbed by the kidney2 • The remaining glucose is reabsorbed by SGLT1 further along the proximal tubule1 • The reabsorbed glucose is then returned to the blood2 37 Adapted from Nair S, Wilding JP. J Clin Endocrinol Metab. 2010;95:34-42. Reference: 1. Nair S, Wilding JP. J Clin Endocrinol Metab. 2010;95:34-42. 2. DeFronzo RA, et al. Diabetes Obes Metab. 2012;14:5-14.
  • 39.
    Glucose Transport inTubular Epithelial Cells G Glucose Na+ Sodium K Potassium BloodLumen S1 Proximal Tubule G Na+ K GLUT2 ATPase SGLT2 High Capacity Low Affinity BloodLumen S3 Proximal Tubule G 2Na+ 2K GLUT1 ATPase SGLT1 Low Capacity High Affinity Adapted from Bakris GL et al. Kidney Int 2009;75:1272-7 Marsenic O. Am J Kidney Dis. 2009;53:875-83
  • 40.
    Glucose Reabsorption ina Nondiabetic Person (Plasma Glucose <10 mmol/L ) Glomerulus Proximal Convoluted Tubule Glucose reabsorption into tissue Early Distal Glucose SGLT1SGLT2 Urine Adapted with permission from Rothenberg PL et al. SGLT = sodium-glucose linked co-transporter. Rothenberg PL et al. Poster presented at EASD 2010; Stockholm, Sweden
  • 41.
    The role ofthe kidney in glucose reabsorption 41 ~180L filtered per day by the kidney1 References: 1. DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab. 2012 Jan;14(1):5-14. 2. Clifford J. Bailey. Medscape Education Diabetes & Endocrinology. The Role of the Kidney in Glucose Control.. CME Released: 02/26/2013 ; Valid for credit through 02/26/2014. A normal kidney A kidney in a patient with type 2 diabetes Average blood glucose of ~100mg/dL2 Average blood glucose of ~150mg/dL2 ~180g of glucose filtered per day2 No increase in SGLT2 cotransporters2 ~250g of glucose filtered per day2  glucose reabsorption and  elimination of glucose in the urine2 Hyperglycaemia Increase in SGLT2 cotransporters2
  • 42.
    Glucose Reabsorption ina Person With T2DM (Plasma Glucose >10 and <13.3 mmol/L) Glomerulus Proximal Convoluted Tubule Increased glucose reabsorption into tissue compared to normal Early Distal Urine Adapted with permission from Rothenberg PL et al. SGLT = sodium-glucose linked co-transporter. Rothenberg PL et al. Poster presented at EASD 2010; Stockholm, Sweden Glucose SGLT1SGLT2
  • 43.
    Effects of SGLT2Inhibitors Inhibition of renal tubular Na+- glucose co-transporter reversal of hyperglycemia reversal of “glucotoxicity” Insulin sensitivity in muscle Insulin sensitivity in liver Gluconeogenesis Improved beta cell function DeFronzo RA, et al. Diabetes Obes Metab. 2012;14(1):5-14.
  • 47.
    Trends in Treatmentof T2DM from 1997 to 2012 in USA Sulfonylureas Insulin GLP-1 agonist
  • 48.
  • 50.
  • 51.
    Treating patients shouldbe to targets with consideration of patients individualization FPG <110 mg/dl FPG <130 mg/dl HbA1c <7.0% HbA1c <7.0% ADA1,2/ EASD2 IDF3 PPG < 160 mg/dl PPG <180 mg/dl 1. American Diabetes Association Diabetes Care 2009;32 (Suppl 1):S1-S97 2. ADA/EASD Consensus guideline. Diabetes Care 2009;32(1): 193-203 3. IDF Treatment Algorithm for People with Type 2 Diabetes. 2011
  • 52.
    Smoking Lifestyle Control blood pressure Education Statin Metformin Aspirin Control blood glucose Individualised careof patients: based on evidence for each intervention Type 2 diabetes management is multifactorial
  • 53.
    peripheral glucose uptake hepatic glucose production pancreatic insulin secretion pancreatic glucagon secretion gut carbohydrate delivery & absorption incretin effect HYPERGLYCEMIA ? Adapted from:Inzucchi SE, Sherwin RS in: Cecil Medicine 2011 Multiple, Complex Pathophysiological Abnormalities in T2DM _ _ + renal glucose excretion
  • 54.
    peripheral glucose uptake hepatic glucose production pancreatic insulin secretion pancreatic glucagon secretion gut carbohydrate delivery & absorption incretin effect HYPERGLYCEMIA ? Adapted from:Inzucchi SE, Sherwin RS in: Cecil Medicine 2011 Multiple, Complex Pathophysiological Abnormalities in T2DM _ _ + renal glucose excretion DA agonists T Z D sMetformin S U sGlinides DPP-4 inhibitors GLP-1R agonists A G I s Amylin mimetics Insulin Bile acid sequestrants
  • 55.
    What’s missing 5 principlesin selecting Antihyperglycemic interventions 1. Efficacy 2. Hypoglycemia 3. Weight 4. Side effects 5. Cost
  • 56.
    Standards of Medical Carein Diabetes — 2016
  • 57.
    Healthy eating, weightcontrol, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-ior or or GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + Figure 2. Anti-hyperglycemic therapy in T2DM: General recommendations Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
  • 58.
    Healthy eating, weightcontrol, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-ior or or GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + Figure 2. Anti-hyperglycemic therapy in T2DM: General recommendations Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
  • 59.
    Healthy eating, weightcontrol, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-ior or or GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + Figure 2. Anti-hyperglycemic therapy in T2DM: General recommendations Diabetes Care 2016;38:140-149; Diabetologia 2015;58:429-442
  • 60.
    Healthy eating, weightcontrol, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-ior or or GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
  • 61.
    Healthy eating, weightcontrol, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-ior or or GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442 HbA1c ≥9% Metformin intolerance or contraindication Uncontrolled hyperglycemia (catabolic features, BG ≥300-350 mg/dl, HbA1c ≥10-12%)
  • 62.
    Healthy eating, weightcontrol, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-i GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin or or or Insulin (basal) + Figure 2A. Anti-hyperglycemic therapy in T2DM: Avoidance of hypoglycemia Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
  • 63.
    Healthy eating, weightcontrol, increased physical activity & diabetes education Metformin high low risk neutral/loss GI / lactic acidosis low If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): Metformin + Metformin + Metformin + Metformin + Metformin + high low risk gain edema, HF, fxs low Thiazolidine- dione intermediate low risk neutral rare high DPP-4 inhibitor highest high risk gain hypoglycemia variable Insulin (basal) Metformin + Metformin + Metformin + Metformin + Metformin + Basal Insulin + Sulfonylurea + TZD DPP-4-i GLP-1-RA Insulin§ or or or or Thiazolidine- dione + SU DPP-4-i GLP-1-RA Insulin§ TZD DPP-4-i GLP-1-RA high low risk loss GI high GLP-1 receptor agonist Sulfonylurea high moderate risk gain hypoglycemia low SGLT2 inhibitor intermediate low risk loss GU, dehydration high SU TZD Insulin§ GLP-1 receptor agonist + SGLT-2 Inhibitor + SU TZD Insulin§ Metformin + Metformin + or or or or SGLT2-i or or or SGLT2-i Mono- therapy Efficacy* Hypo risk Weight Side effects Costs Dual therapy† Efficacy* Hypo risk Weight Side effects Costs Triple therapy or or DPP-4 Inhibitor + SU TZD Insulin§ SGLT2-i or or or SGLT2-i or DPP-4-i If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors): If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i: Metformin + Combination injectable therapy‡ GLP-1-RAMealtime Insulin Insulin (basal) + or or or Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442 Figure 2B. Anti-hyperglycemic therapy in T2DM: Avoidance of weight gain
  • 64.
    1-Aspirin therapy forwomen aged 50 and older(changed from women ›60 previously) 2-antiplatlet use in patients younger than 50 with multiple risk factor 3- addition of Ezetimibe to moderate-intensity statin therapy in patient with diabetes based on Recent IMPROVED-IT trial. 4-- some linguistic shift as ASCVD is more specific than CVD, And Diabetic Kidney Disease DKD instead of nephropathy. 5-tailoring treatment for vulnerable populations with diabetes ,such as HIV infection, Mental illness Food insecurity. What is new in ADA 2016?
  • 65.
    ● Diabetes treatmentmust be individualized, patient-centered, and culturally appropriate. ● In Asian Americans, consider DM testing in adults of any age with 1 risk factor and a BMI ≥23. ● To decrease disparities, all providers and groups are encouraged to use the National Quality Forum’s National Voluntary Consensus Standards for Ambulatory Care— Measuring Healthcare Disparities Tailoring Treatment American Diabetes Association Standards of Medical Care in Diabetes. Strategies for improving diabetes care. Diabetes Care 2016; 39 (Suppl. 1): S6-S12
  • 66.
    ● Lack ofhealth insurance ● Food insecurity (FI) o Carefully evaluate hyperglycemia and hypoglycemia and propose solutions A o Recognize that homelessness and poor literacy often occur with food insecurity; appropriate resources should be made available for patients with diabetes. A Health Disparities American Diabetes Association Standards of Medical Care in Diabetes. Strategies for improving diabetes care. Diabetes Care 2016; 39 (Suppl. 1): S6-S12
  • 67.
    1. Intensive glucosecontrol is not advised for the improvement of poor cognitive function in hyperglycemic individuals with T2DM. B 2. In individuals with poor cognitive function or severe hypoglycemia, glycemic therapy should be tailored to avoid significant hypoglycemia. C Cognitive Dysfunction American Diabetes Association Standards of Medical Care in Diabetes. Strategies for improving diabetes care. Diabetes Care 2016; 39 (Suppl. 1): S6-S12
  • 68.
    3. In individualswith diabetes at high CVD risk, the cardiovascular benefits of statin therapy outweigh the risk of cognitive dysfunction. A 4. If a second-generation antipsychotic medication is prescribed, changes in weight, glycemic control, and cholesterol levels, should be carefully monitored and the treatment regimen reassessed. C Cognitive Dysfunction (2) American Diabetes Association Standards of Medical Care in Diabetes. Strategies for improving diabetes care. Diabetes Care 2016; 39 (Suppl. 1): S6-S12
  • 69.
    ● Screen patientswith HIV for diabetes and prediabetes before starting antiretroviral (ARV) therapy, and 3 months after starting or changing it. E ● If initial screening results are normal, check fasting glucose annually. E ● If prediabetes is detected, continue to measure levels every 3-6 months to monitor for progression to diabetes. E Human Immunodeficiency Virus (HIV) American Diabetes Association Standards of Medical Care in Diabetes. Strategies for improving diabetes care. Diabetes Care 2016; 39 (Suppl. 1): S6-S12
  • 70.
    New section ofObesity ,covering life style modofication,pharmacological management & bariatric surgery has been added. Cont. What is new in ADA 2016?
  • 71.
    ● Guidelines supportgastric banding, gastrectomy, and bypass as effective treatments for overweight T2DM patients. ● In 72% of patients, bariatric surgery helped achieve near- or complete normalization of glycemia 2 yrs post- surgery. ● In one meta-analysis, gastric banding resulted in less weight loss than gastrectomy or Roux-en-Y. Bariatric Surgery American Diabetes Association Standards of Medical Care in Diabetes. Obesity management for the treatment of type 2 diabetes. Diabetes Care 2016; 39 (Suppl. 1): S47-S51
  • 72.
    ● Bariatric surgerymay be considered for adults with BMI >35 and T2DM, especially if diabetes or associated comorbidities are difficult to control with lifestyle & medications. B ● Patients with T2DM who have undergone bariatric surgery need lifelong lifestyle support and annual medical monitoring, at a minimum. B Recommendations: Bariatric Surgery American Diabetes Association Standards of Medical Care in Diabetes. Obesity management for the treatment of type 2 diabetes. Diabetes Care 2016; 39 (Suppl. 1): S47-S51
  • 73.
    ● Although smalltrials have shown glycemic benefit of bariatric surgery in patients with T2DM and BMI 30–35, there is currently insufficient evidence to generally recommend surgery in patients with BMI ≤35. E Recommendations: Bariatric Surgery American Diabetes Association Standards of Medical Care in Diabetes. Obesity management for the treatment of type 2 diabetes. Diabetes Care 2016; 39 (Suppl. 1): S47-S51
  • 74.
    ● Costly ● Someassociated risks ● Outcomes vary ● Patients undergoing bariatric surgery may be at higher risk for substance abuse including drug and alcohol use and cigarette smoking. Disadvantages of bariatric surgery American Diabetes Association Standards of Medical Care in Diabetes. Obesity management for the treatment of type 2 diabetes. Diabetes Care 2016; 39 (Suppl. 1): S47-S51
  • 77.
    Despite treatment advances,mean HbA1C in type 2 diabetes is elevated in most countries Canada 7.36–8.7%11 Latin America 7.6%1 US 7.2%7 China 9.5%11 India 8.7–9.6%9,11 Japan 7.05–9.6%11 Korea 7.9–8.7%4 Russia 9.6%11 Spain 9.2%8 Sweden 8.7%3 Turkey 10.6%3 UK 8.510–9.8%2 Germany 8.42–9.2%8 Greece 8.911–9.7%3,8 Italy 8.4%11 Poland 9.0%11 Portugal 9.7%3 Romania 9.9%3 1. Lopez Stewart et al. Rev Panam Salud Publica 2007;22:12–20; 2. Kostev & Rathmann Primary Care Diabetes 2013;7:229–33; 3. Oguz et al. Curr Med Res Opin 2013;29:911–20; 4. Ko et al. Diab Med 2007;24:55–62; 5. Arai et al. Diab Res Clin Prac 2009;83:397–401; 6. Harris et al. Diabetes Res Clin Pract 2005;70:90–7; 7. Hoerger et.al. Diabetes Care 2008;31:81–6; 8. Liebl et al. Diab Ther 2012;3:e1–10; 9. Shah et al. Adv Ther 2009;26:325–35; 10. Blak et al. Diab Med 2012;29:e13–20; 11. Valensi et al. Int J Clin Pract 2008;62:1809–19
  • 78.
    Every day exercise Choosingthe …….. Drug for the ………..….. patientbest Appropriate
  • 79.