confluence module 2 new drs final version

Type-2 Diabetes Mellitus: Path Ahead In Management

.

Learning objectives

• To evaluate the patient with type 2 diabetes and set treatment goals

• To apply a guideline-based approach for effective management of type 2 DM

• To educate and empower the patient on management of type 2 diabetes

• To choose appropriate pharmacological management based on patient needs

• To detect comorbid conditions associated with diabetes and address to the same

Evaluation of diabetic patients

• A comprehensive evaluation is essential for optimal management of type 2 DM

• The aim of initial evaluation is to1:• Detect the presence of diabetes complications• Review previous treatment and glycaemic control in patients with established

diabetes• Formulate treatment plan based on individual needs• Provide a basis for continuing care

1. American Diabetes Association. Standards of Medical Care in Diabetes--2011. Diabetes Care. 2010;34(suppl 1):S11-S61.

Diabetes evaluation

• Components of diabetes evaluation include1:• Detailed medical history• Physical examination• Laboratory evaluation• Referrals

• Management of diabetes requires a team of professionals1:• Physicians• Nurse practitioners• Physician assistants• Dieticians• Pharmacists• Other health care faculty


Treatment goals

1. American Diabetes Association. Standards of Medical Care in Diabetes--2011. Diabetes Care. 2010;34(suppl 1):S11-S61.2. Blonde L. Current antihyperglycemic treatment guidelines and algorithms for patients with type 2 diabetes mellitus. Am J Med. 2010;123(3):S12-S18.3. ICMR guidelines. Pharmacological treatment for diabetes. www.icmr.nic.in/guidelines_diabetes/section7.pdf. Accessed June 28, 2011.4. International Diabetes Federation, 2005. Global guidelines for type 2 diabetes. www.idf.org/webdata/docs/IDF%20GGT2D.pdf. Accessed June 28, 2011.

• Normalising glycaemia reduces diabetes-related mortality and morbidity1

• Guidelines suggest the following treatment goals2,3,4:

• Treatment goals should be individualised for optimal glycaemic control2

Target treatment goal ADA IDF ICMR

HbA1c <7% <6.5% <7%

Preprandial glucose 70–130 mg/dL <110 mg/dL 80–110 mg/dL

Postprandial glucose <180 mg/dL <145 mg/dL 120–140 mg/dL

Target HbA1c goat Patient types*

HbA1c <7.0% General nonpregnant adult population for the delay or prevention of•Microvascular disease•Macrovascular disease

Lower than the general goal of HbAIc <7.0% (if possible without significant hypoglycaemia or other treatment-related adverse events)

Patients with•Short duration of diabetes•Long life expectancy•No significant cardiovascular disease

Less stringent than the general goal of HbA1c <7.0% Patients with•History of severe hypoglycaemia•Limited life expectancy•Advanced micro- or macrovascular complications•Extensive comorbidities•Long-standing diabetes in whom the general goal has been difficult to attain despite diabetes self-management education, appropriate glucose monitoring and effective doses of multiple glucose-lowering agents including insulin

HbA1c, haemoglobin A1c.*On the basis of analyses of data from clinical trials in diabetes as presented in a position statement of the American Diabetes Association (ADA), American College of Cardiology (ACC) Foundation, and the American Heart Association (AHA).

http://www.icmr.nic.in/guidelines_diabetes/section7.pdf





http://www.idf.org/webdata/docs/IDF%20GGT2D.pdf





Guideline-based approach: The ADA

• The ADA proposed two-tier algorithm for treatment1:

• Tier 1: Well-validated treatments• Tier 2: Less-validated treatments

• Over a period of time, most patients require combination of drugs2

1. American Diabetes Association. Standards of Medical Care in Diabetes--2011. Diabetes Care. 2010;34(suppl 1):S11-S61.2. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes

care. 2009;32(1):193.

TIER 1: Well-validated core therapies

At Diagnosis: Lifestyle + Metformin

Lifestyle + Metformin +Basal Insulin

Lifestyle + Metformin +Sulfonylureaa

Lifestyle + Metformin +Intensive Insulin

TIER 2: Less well-validated therapies

STEP 1 STEP 2 STEP 3

Lifestyle + Metformin + PioglitazoneNo hypoglycaemia, weight loss, nausea/vomiting

Lifestyle + Metformin + GLP-1 Agonistb

No hypoglycaemia, weight loss, nausea/vomiting

Lifestyle + Metformin + Pioglitazone+

Sulfonylureaa

Lifestyle + Metformin +Basal Insulin

American Diabetes Association/European Association for the Study of Diabetes AlgorithmGLP-1, glucagon-like peptide-1. aSulfonylureas other than glibenclamide (glyburide) or chlorpropamide; b Insufficient clinical use to be confident regarding safety.

Guideline-based approach: The IDF

According to the IDF1:• First-line therapy includes

lifestyle measures and metformin monotherapy

• Second-line treatments include • Combination of metformin and

basal insulin—most effective • Combination of metformin and

sulfonylurea—cost-effective

• Insulin-based regimens are preferred when lifestyle + oral agents fail

1. International Diabetes Federation, 2005. Global guidelines for type 2 diabetes. www.idf.org/webdata/docs/IDF%20GGT2D.pdf. Accessed June 28, 2011.

Preferred Regimens Alternative Regimens

3

MET, metformin; SU, sulfonylureaMDI, multiple daily injectionαGI, alpha-glucosidase inhibitor

TZD, thiazolidinedioneMEG, meglitinideCHF, congestive heart failure

Diet + exercise + METTitrate MET to maximallyeffective dose over 1–2

months, as tolerated

Most effective:MET + INS

Least expensive:MET + SU

MET + SU + TZD

Continue MET ± SUAdd glargine or detemir, 1/d

MET + biphasic insulin, 2/d

MD3I basal-bolus

SU

MET + TZD

Consider substituting or addingMEG or αGI if MET or SFU not tolerated

SU + TZD

Continue MET ± SUAdd NPH insulin

Continue MET ± TZDAdd basal insulin

Pump

Continue MET ± SU ± αGI Add basal insulin

Caution: Hypoglycaemia risk increased with NPH insulin

Caution: (1) TZD + insulin increases risk of oedema or CHF (2) TZD + insulin not approved in all countries






Guideline-based approach: The ICMR

• As per the ICMR1:• Management is based on obese, nonobese and lean body type• Lifestyle interventions are an integral part of management

1. ICMR guidelines. Pharmacological treatment for diabetes. www.icmr.nic.in/guidelines_diabetes/section7.pdf. Accessed June 28, 2011.

Lifestyle interventionObese Lifestyle intervention

Severe hyperglycaemia Moderate hyperglycaemia Lifestyle + metformin Lifestyle, sulfonylurea

Newly diagnosed type 2 diabetes

Nonobese

Controlled

Insulin Lifestyle + sulfonylurea or meglitinides or glitazone Uncontrolled Uncontrolled

Uncontrolled Addition of sulfonylurea or meglitinides or glitazone or insulin

Add metformin

Insulin ± combination of antidiabetic drugs

Components of diabetes care

• Comprehensive management of type 2 DM includes1:• Optimal glycaemic control• Management of diabetic complications • Management of other comorbidities

1. Fauci A, Braunwald E, Kasper D, et al. Harrison's Manual of Medicine. 17th ed. New York: McGraw-Hill Professional; 2009:205-214.

Management oftype 2 DM

Glycaemic control•Diet/lifestyle•Exercise•Medication

Treat associatedconditions•Dyslipidaemia•Hypertension•Obesity•Coronary heart disease

Screen for/managecomplicationsof diabetes•Retinopathy•Cardiovascular disease•Nephropathy•Neuropathy•Other complications

Management of type 2 DM—nonpharmacologic approach

• Type 2 DM management: • Nonpharmacologic—lifestyle measures• Pharmacologic—oral hypoglycaemics and insulin

• Lifestyle management—integral part of therapy• Diet • Physical exercise• Weight management

• Goals of diet management or medical nutrition therapy (MNT)1:• To achieve and maintain ideal body weight• To achieve euglycaemia and appropriate lipid profile goals• To prevent and postpone the complications of diabetes• To provide optimal nutrition in special situations associated with diabetes such as:

• Pregnancy and lactation• Growth and old age• Comorbidities such as hypertension and other catabolic illnesses

1. ICMR guidelines. Non-pharmacological management of diabetes. http://www.icmr.nic.in/guidelines_diabetes/section6.pdf. Accessed June 28, 2008.

Medical nutrition therapy (MNT)

• MNT recommended based on:• Individual’s background and preferences • Dietician’s opinion

• Total calorie intake is dependent on:• Physical activity and nutritional status• Change in calorie intake—not >500 kcal/d of deficit

• Total calorie distribution: balanced combination of carbs, proteins and fats1,2

• Carbohydrates—55%–65% • Avoid sugar, honey, jaggery and sweets• Encourage cereals, mixed grains, whole pulses, salads, soybeans

• Proteins—10%–15%• Source: Vegetables, low fat milk/milk products, fish and lean meat

• Fat—20%–25%• Saturated fat: <7%• MUFA and PUFA rich

1. American Diabetes Association. Standards of Medical Care in Diabetes--2011. Diabetes Care. 2010;34(suppl 1):S11-S61.2. ICMR guidelines. Non-pharmacological management of diabetes. http://www.icmr.nic.in/guidelines_diabetes/section6.pdf. Accessed June 28, 2008.

Medical nutrition therapy (MNT)

• Diet rich in fibre with one to two servings of fruit• Common salt—up to 6 g/d is allowed• Alcohol and tobacco—to be avoided• Artificial sweeteners to be allowed in limited quantities

• Dietary recommendations in special situations1:• Nephropathy: Dietary protein restricted to 0.6 g/kg and salt to 4 g/d• Hypertension: Salt intake should be restricted to minimum of 1.5 g/d (as per

DASH diet)• Dyslipidaemia: Total fat intake ↓ and MUFA and dietary fibre to be ↑ and

saturated fatty acids ↓• Infections and acute illness: Avoid fasting and provide adequate calorie intake


Physical exercise

• Physical exercise—multiple benefits1

• Carefully assess patients for individual capacities and disabilities• Stepwise increase in aerobic exercise helps in improving:

• Regular exercise recommended• 30 to 60 min/d of brisk walk or 150 min/wk of moderate intensity aerobic exercise• Yoga and pranayama are beneficial


Physical exercise

Strenuous physical activity to be avoided in1:• Coronary artery disease: Exercise regimen carefully prescribed

only after cardiac evaluation• Proliferative diabetic nephropathy: Diving, weight lifting or

bending avoided to prevent vitreous haemorrhage or retinal detachment

• Diabetic nephropathy: Reduced exercise capacity• Peripheral neuropathy: Observe for any blisters or damage to

the feet before and after exercise


Weight management1

• Overweight: >120% of ideal body weight• Underweight: <90% of ideal body weight• Ideal body weight = (Height in cm−100) x 0.9• Weight-loss recommended for:

• Overweight and obese• Weight loss leads to :

• Reduction in insulin resistance• Reduction in HbA1c• Reduction in cardiovascular risk factors because of improved lipid profile

• Weight loss requires:• Dietary modification• Physical activity• Motivation and behavioural modification through professionals2

1. ICMR guidelines. Non-pharmacological management of diabetes. http://www.icmr.nic.in/guidelines_diabetes/section6.pdf. Accessed June 28, 2008.2. American Diabetes Association. Standards of Medical Care in Diabetes--2011. Diabetes Care. 2010;34(supplement 1):S11-S61.

Diabetes self-management education (DSME)1,2

• DSME improves quality of life through patient initiative• DSME should include psychological support• DSME helps in:

• Achieving glycaemic control• Prevention and management of complications• Following nutrition and physical activity recommendations• Facilitating psychosocial adjustment• Managing diabetes cost-effectively • Managing disease in special situations: pregnancy and comorbidities

1. American Diabetes Association. Standards of Medical Care in Diabetes--2011. Diabetes Care. 2010;34(suppl 1):S11-S61. 2. Blonde L. Current antihyperglycemic treatment guidelines and algorithms for patients with type 2 diabetes mellitus. Am J Med. 2010;123(3):S12-S18.

DSME

• DSME imparts—knowledge, skill and ability to self-manage diabetes1

• DSME helps patients in2

• Informed decision making• Adhering to treatment and

glucose monitoring recommendations

• Self care• Problem solving• Co-ordinating with health care

team to obtain optimal results1. American Diabetes Association. Standards of Medical Care in Diabetes--2011. Diabetes Care. 2010;34(suppl 1):S11-S61. 2. Blonde L. Current antihyperglycemic treatment guidelines and algorithms for patients with type 2 diabetes mellitus. Am J Med. 2010;123(3):S12-S18.

Glucose monitoring—self-monitoring of blood glucose (SMBG)1,2

• Regular glucose monitoring is essential to:• Assess glycaemic control• Monitor treatment effectiveness

• Glucose monitoring is done with:• Self-monitoring of blood glucose• HbA1c

• SMBG should be available:• To all newly diagnosed type 2 DM as a part of DSME• To all patients on multiple insulin injections

1. American Diabetes Association. Standards of Medical Care in Diabetes--2011. Diabetes Care. 2010;34(suppl 1):S11-S61. 2. International Diabetes Federation, 2005. Global guidelines for type 2 diabetes. www.idf.org/webdata/docs/IDF%20GGT2D.pdf. Accessed June 28, 2011.

The ADA recommendations—SMBG1

• SMBG should be carried out three to four times a day by those on multiple insulin injections

• SMBG acts as guide for successful therapy in patients with:• Less frequent insulin injections• Noninsulin therapy • Medical nutrition therapy

• Ongoing SMBG is helpful in patients on oral hypoglycaemics to:• Provide information on hypoglycaemia• Assess fluctuation in glucose as a result of medication and lifestyle changes• Monitor changes during intercurrent illness

• Intermittent SMBG advised for people who are neither on insulin or oral antidiabetic agents to• Assess glucose fluctuations because of lifestyle

• Monitor changes in glucose during intercurrent illness


Glucose monitoring—HbA1c1,2

• HbA1c should be performed • Two times a year in those who have achieved the target• Four times a year in those who have not achieved the target or whose

treatment has been changed

• HbA1c strongly predicts diabetic complications• A HbA1c goal of 6.5%–7% recommended for optimal control of diabetes based

on individual needs• HbA1c quantifies the risk of complications in diabetes

1. International Diabetes Federation, 2005. Global guidelines for type 2 diabetes. www.idf.org/webdata/docs/IDF%20GGT2D.pdf. Accessed June 28, 2011. 2. American Diabetes Association. Standards of Medical Care in Diabetes--2011. Diabetes Care. 2010;34(Suppl 1):S11-S61.

The ADA recommendations1

• Properly instruct on the techniques of SMBG and use of the data to adjust treatment

• SMBG should be used to:• Assess the individual response to therapy• Assess glycaemic targets and • Adjust medications

• Continuous glucose monitoring (CGM) is another method for monitoring in patients on intensive insulin regimens

• CGM may be a supplemental tool to SMBG:• In patients with hypoglycaemia unawareness and• In those with frequent hypoglycaemic episodes

• CGM lessens the time spent in hypo- and hyperglycaemia

1. American Diabetes Association. Standards of Medical Care in Diabetes--2011. Diabetes Care. 2010;34(suppl ):S11-S61.

Psychological care in diabetes1,2

• Psychosocial care—important part of medical care in diabetes• Psychosocial assessment includes evaluation of:

• These assessments to be made:• At diagnosis, follow-up, during hospitalisation, or at diagnosis of diabetic

complications

1. American Diabetes Association. Standards of Medical Care in Diabetes--2011. Diabetes Care. 2010;34(suppl 1):S11-S61.2. International Diabetes Federation, 2005. Global guidelines for type 2 diabetes. www.idf.org/webdata/docs/IDF%20GGT2D.pdf. Accessed June 28, 2011.

Pharmacologic therapy

Oral antidiabetic drugs:• Biguanides• Sufonylureas• Alpha-glucosidase inhibitors• Meglitinide analogues• Thiazolidinediones• Incretin based therapy: GLP-1 agonists, DPP-IV inhibitors

1. Blonde L. Current antihyperglycemic treatment guidelines and algorithms for patients with type 2 diabetes mellitus. Am J Med. 2010;123(3):S12-S18.

Mechanism of action of oral antidiabetics

• Decreases hepatic glucose production: Biguanides, thiazolidinediones

• Increases muscle glucose uptake: Thiazolidinediones, biguanides

• Stimulates insulin secretion: Repaglinide or sulfonylureas • Retards carbohydrate absorption: Alpha-glucosidase inhibitors• Corrects insulin deficiency: Insulin or insulin analogues

1. Blonde L. Current antihyperglycemic treatment guidelines and algorithms for patients with type 2 diabetes mellitus. Am J Med. 2010;123(3):S12-S18.

Biguanides1,2,3

• Metformin—↓ hepatic glucose output—↓ FPG —↓ insulin resistance• Most common and efficacious agents used • Weight neutral—preferred in obese• Reduces HbA1c by approximately 1.5%• Reduces BP and improves lipid profile as well• ↓ micro- and macrovascular complications as well• Lacks hypoglycaemic effect• Contraindicated in renal dysfunction (GFR <30 mL/min)—

lactic acidosis1. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes

care. 2009;32(1):193.2. Fauci A, Braunwald E, Kasper D, et al. Harrison's Manual of Medicine. 17th ed. New York: McGraw-Hill Professional; 2009:205-214.3. Campbell RK. Type 2 diabetes: where we are today: an overview of disease burden, current treatments, and treatment strategies. J Am Pharm Assoc. 2009;49(0):S3-S9.

Sulfonylureas1,2,3

• SUs—insulin secretagogues• Especially effective in diabetes <5 years duration• ↓ HbA1c by 1.5%• Long-acting agents—glimepiride and glipizide—faster and

sustained action• Well tolerated—long-term safety data available• Cost-effective agents• Disadvantages—risk of hypoglycaemia (less common with

2nd gen SUs) and weight gain1. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes

care. 2009;32(1):193.2. Fauci A, Braunwald E, Kasper D, et al. Harrison's Manual of Medicine. 17th ed. New York: McGraw-Hill Professional; 2009: 205-214.3. Campbell RK. Type 2 diabetes: where we are today: an overview of disease burden, current treatments, and treatment strategies. J Am Pharm Assoc. 2009;49(0):S3-S9.

Alpha-glucosidase inhibitors

Alpha-glucosidase inhibitors: acarbose, miglitol and volglibose• Act by delaying the digestion of carbohydrates in the intestine• Effectively control postprandial hyperglycaemia as well as fasting

plasma glucose • No secondary failure with glucosidase inhibitors• Reduce HbA1c by <1% depicting long-term glycaemic control• Benefits:

• Reduce progression of prediabetes• Provide cardiovascular benefits by reducing the risk of developing hypertension, MI • Reduce other cardiovascular events such as angina, heart failure and stroke

• Acarbose has demonstrated benefits in dyslipidaemic patients• Do not cause hypoglycaemia and weight gain• Disadvantages include gastrointestinal side effects


Glinides and glitazones

Glinides (repaglinide and nateglinide)2,3

•Repaglinide and nateglinide—↓ HbA1c by 0.5%–1.5%•Control prandial hyperglycaemia•Faster acting and cause hypoglycaemia and weight gain

Glitazones (pioglitazone and rosiglitazone)1,2

•Insulin sensitisers; effective in glycaemic control•Reduce insulin resistance but increase plasma lipid levels (total, LDL and HDL)•↓ HbA1c by up to 1.5%• Side effects—weight gain, peripheral oedema, CHF and macular oedema1. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes

care. 2009;32(1):193.2. Fauci A, Braunwald E, Kasper D, et al. Harrison's Manual of Medicine. 17th ed. New York: McGraw-Hill Professional; 2009: 205-214.3. Campbell RK. Type 2 diabetes: where we are today: an overview of disease burden, current treatments, and treatment strategies. J Am Pharm Assoc. 2009;49(0):S3-S9.

Incretin based therapy

GLP-1 agonists (exenatide and liraglutide)1,2:• Act by glucose-stimulated insulin secretion (incretin effect)

• Suppress glucagon secretion • Decrease gastric motility

• Exenatide, a GLP-1 agonist • Available as an injectable• Recommended to be used with other agents such as metformin or

sulfonylureas• ↓ HbA1c by 0.5%–1%• Modest efficacy: Do not promote weight gain• Common side effects: Gastrointestinal• Require daily one or two subcutaneous administration

1. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes care. 2009;32(1):193.

2. Fauci A, Braunwald E, Kasper D, et al. Harrison's Manual of Medicine. 17th ed. New York: McGraw-Hill Professional; 2009: 205-214.

Incretin based therapy

• DPP-IV inhibitors (sitagliptin, vildagliptin, saxagliptin)1,2

• Act by inhibiting the degradation of native GLP-1 and enhancing incretin effect• Reduce postprandial blood glucose• Reduce HbA1c by 0.6%–0.9%• Advantages—minimal risk of hypoglycaemia, weight gain • Interference with immune function and increase in upper respiratory

infections are some of the concerns with DPP-IV inhibitors

1. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes care. 2009;32(1):193.

2. Fauci A, Braunwald E, Kasper D, et al. Harrison's Manual of Medicine. 17th ed. New York: McGraw-Hill Professional; 2009: 205-214.

Combination therapy for type 2 DM

• Diabetes—progressive disorder—↓β cell function1

• Glycaemic control deteriorates• Most patients require combination therapy

• Combination therapy2,3

• Drugs with synergistic effect and different MOA to be chosen• Metformin and sulfonylurea combination—most effective• Metformin and glucosidase inhibitors—improve long-term glycaemic control• Insulin can be added to oral agents for better glycaemic control• Three drug combination—metformin + SU + glitazone—if two drug

combination is not adequate

1. Turner RC. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999;281(21):2005-2012.

2. . Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. Diabetes Care. 2009;32(1):193.

3. Phillips P, Karrasch J, Scott R, Wilson D, Moses R. Acarbose improves glycemic control in overweight type 2 diabetic patients insufficiently treated with metformin. Diabetes Care. 2003;26:269-273.

Oral combination therapy

1. Patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999;281(21):2005-2012.2. González-Ortiz M, Guerrero-Romero JF, Violante-Ortiz R, et al. Efficacy of glimepiride/metformin combination versus glibenclamide/metformin in patients with uncontrolled type 2

diabetes mellitus. J Diabetes Complications. 2009;23(6):376-379.3. Lewin A, Lipetz R, Wu J, Schwartz S. Comparison of extended-release metformin in combination with a sulfonylurea (glyburide) to sulfonylurea monotherapy in adult patients with

type 2 diabetes: a multicenter, double-blind, randomized, controlled, phase III study. Clin Ther. 2007;29(5):844-855.4. Kaku K. Efficacy and safety of therapy with metformin plus pioglitazone in the treatment of patients with type 2 diabetes: a double-blind, placebo-controlled, clinical trial. Curr Med

Res Opin. 2009;25(5):1111-1119.5. Karamanos B, Thanopoulou A, Drossinos V, et al. Study comparing the effect of pioglitazone in combination with either metformin or sulphonylureas on lipid profile and glycaemic

control in patients with type 2 diabetes (ECLA). Curr Med Res Opin. 2010;(0):303-313.


• Metformin + Acarbose• Improves glycaemic control in those on metformin alone• Safe and useful in overweight patients• Delays onset of diabetic complications• Benefits:

• Positive effects on hyperinsulinaemia, body weight and lipid profile• Better safety profile• Lack of hypoglycaemia

1. Phillips P, Karrasch J, Scott R, Wilson D, Moses R. Acarbose improves glycemic control in overweight type 2 diabetic patients insufficiently treated with metformin. Diabetes Care. 2003;26:269-273.


• Sulfonylurea + Glitazone1,2

• Provides better glycaemic control and improves lipid profile and insulin resistance

• May be better than metformin and sulfonylurea combination• Addition of pioglitazone to sulfonylurea (glimepiride) provides better BP

control as well

• Triple therapy with sulfonylurea + glitazone + metformin3 • Effective in those with inadequately controlled glycaemia with metformin and

glitazone• Shown to have lower risk of hypoglycaemia

1. Karamanos B, Thanopoulou A, Drossinos V, et al. Study comparing the effect of pioglitazone in combination with either metformin or sulphonylureas on lipid profile and glycaemic control in patients with type 2 diabetes (ECLA). Curr Med Res Opin. 2010;(0):303-313.

2. Dorkhan M, Frid A. A review of pioglitazone HCL and glimepiride in the treatment of type 2 diabetes. Vasc Health Risk Manag. 2007;3(5):721.3. Roberts VL, Stewart J, Issa M, Lake B, Melis R. Triple therapy with glimepiride in patients with type 2 diabetes mellitus inadequately controlled by metformin and a thiazolidinedione:

results of a 30-week, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2005;27(10):1535-1547.


• Combination of incretin-based treatment with oral agents1,2,3,4

• Addition of exenatide to metformin recommended by the ADA as a tier 2 approach

• Addition of exenatide to metformin/sulfonylurea in those with uncontrolled hyperglycaemia results in: • Significant improvement in HbA1c • ↓ in body weight • ↓ in PPBG excursions

• DPP-IV inhibitors (sitagliptin) + metformin—superior efficacy over metformin alone—as initial agents in type 2 diabetes• Similarly, vildagliptin + pioglitazone—effective in:

• Preserving beta-cell function • Improving insulin resistance

1. Campbell RK. Type 2 diabetes: where we are today: an overview of disease burden, current treatments, and treatment strategies. J Am Pharm Assoc. 2009;49(0):S3-S9.2. Barnett AH, Burger J, Johns D, et al. Tolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or

a sulfonylurea: a multinational, randomized, open-label, two-period, crossover noninferiority trial. Clin Ther. 2007;29(11):2333-2348.3. Olansky L, Reasner C, Seck TL, et al. A treatment strategy implementing combination therapy with sitagliptin and metformin results in superior glycemic control versus metformin

monotherapy due to a low rate of addition of antihyperglycemic agents. Diabetes Obes Metab.4. Derosa G, Maffioli P, Ferrari I, et al. Effects of one year treatment of vildagliptin added to pioglitazone or glimepiride in poorly controlled type 2 diabetic patients. Horm Metab Res.

2010;42(9):663-669.

Insulin therapy

• Role of insulin in type 2 DM1

1. Drab S. Translating clinical guidelines into clinical practice: role of the pharmacist in type 2 diabetes management. J Am Pharm Assoc. 2009;49(6):e152-e162.

Insulin therapy

• Insulin reduces very high levels of blood glucose vs oral agents• Only initial treatment of choice in newly diagnosed diabetes

• When HBA1c >10% or FBG >250 mg/dL • When HbA1c >8.5% in spite of oral agents

• Insulin source: pork pancreas/recombinant DNA technology/chemical modification1,2

• Types: Based on time and duration of action1,2:• Rapid-acting: Insulin lispro, aspart and glulisine• Short-acting: Regular insulin• Intermediate-acting: NPH insulin• Long-acting: Insulin glargine and detemir

1. Drab S. Translating clinical guidelines into clinical practice: role of the pharmacist in type 2 diabetes management. J Am Pharm Assoc. 2009;49(6):e152-e162.2. Nolte SM, Karam HJ. Pancreatic hormones & antidiabetic drugs. In: Katzung BG, ed. Basic and Clinical Pharmacology. 10th ed. 2007;683-705.

• Maintenance insulins1

• Replacement for basal insulin secretion between meals and during sleep

• Long-acting: Insulin glargine, detemir • Provides peakless action • Action starts within 1–2 hrs and

lasts for up to 24 hrs• Reduces risk of hypoglycaemia

• Intermediate-acting insulin (NPH)• Can be mixed with mealtime

insulin• Higher risk of nocturnal

hypoglycaemia

Insulin therapy

• Meal time insulins1,2

• Control prandial hyperglycaemia• Regular insulin

• Given 30 min before meals• Effective in fluctuating insulin

requirements • Risk of early postprandial

hyperglycaemia and late hypoglycaemia

• Rapid-acting insulins • Faster onset and shorter duration• Mimic endogenous mealtime

secretion• Lesser hypoglycaemia and flexible

dosing time1. Sucher JB, Sucher JA, Clapp P. Managing hypoglycemia in type 2 diabetes mellitus: focus on optimal insulin use. https://secure.pharmacytimes.com/lessons/201010-CS2A.asp.Accessed June 28, 2011. 2. Drab S. Translating clinical guidelines into clinical practice: role of the pharmacist in type 2 diabetes management. J Am Pharm Assoc. 2009;49(6):e152-e162.

Dosing and titration

• General rule1—‘start slow- go slow’—simple basal insulin regimen recommended—start with 10 units—modify the dosage if FBS is beyond

normal range—monitor for hypoglycaemia through regular monitoring

• If basal insulin does not control glycaemia—add mealtime or rapid-acting insulins

• Start with four units—↑ the dosage every 3 days by two units—to reach the target2

• Insulin regimens require modification during acute illness and hospitalisation2

1. Sucher JB, Sucher JA, Clapp P. Managing hypoglycemia in type 2 diabetes mellitus: focus on optimal insulin use. https://secure.pharmacytimes.com/lessons/201010-CS2A.asp. Accessed June 28, 2011.

2. Henske JA, Griffith ML, Fowler MJ. Initiating and titrating insulin in patients with type 2 diabetes. Clin Diabetes. 2009;27(2):72.

Adverse effects of insulin

• Hypoglycaemia—most common side effect• Occurs because of delay in taking meals, unusual physical exertion or

fluctuating insulin dosage• Hypoglycaemic unawareness seen in patients with frequent hypoglycaemia• Prompt treatment required1

• Weight gain• Should be addressed to ↓ the risk of metabolic and CV complications• Newer insulin analogues have lesser chances of weight gain2

• Allergy and dystrophy• Immediate type hypersensitivity —anti-IgE antibodies• Rare with newer insulins3

1. Drab S. Translating clinical guidelines into clinical practice: role of the pharmacist in type 2 diabetes management. J Am Pharm Assoc. 2009;49(6):e152-e162.2. Henske JA, Griffith ML, Fowler MJ. Initiating and titrating insulin in patients with type 2 diabetes. Clin Diabetes. 2009;27(2):72.3. Nolte SM, Karam HJ. Pancreatic hormones & antidiabetic drugs. In: Katzung BG, ed. Basic and Clinical Pharmacology. 10th ed. 2007;683-705.

Burden of comorbidities in diabetes

• Comorbidities in DM• DM—a risk factor for CV events• Hypertension, dyslipidaemia, metabolic syndrome and coronary heart disease

—common• Screening and treatment required1

• Dyslipidaemia and diabetes• High prevalence of dyslipidaemia among patients with diabetes in India

especially ‘mixed dyslipidaemia’• Promptly treated to reduce CV complications2

• Hypertension and diabetes• Extremely common comorbid condition in diabetes3

• BP goal in this population: <130/80 mm Hg1

1. American Diabetes Association. Standards of Medical Care in Diabetes--2011. Diabetes Care. 2010;34(suppl 1):S11-S61.2. Gupta S. Editorial. Int J Diab Dev Ctries. 2004;24(3):58-64. 3. American Diabetic Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003;26(1):s80-s82.

Burden of comorbidities in diabetes

• Diabetes and metabolic syndrome• Metabolic syndrome—a constellation of cardiovascular risk factors1 • High prevalence of metabolic syndrome in India • Requires aggressive management2

• Diabetes and cerebrovascular diseases (CVD)• Diabetes ↑ the risk of CVD by twofold compared with nondiabetic population• Prothrombotic state, ↑ platelet aggregation ↑ risk of stroke3

1. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure - Complete Report. National Heart, Lung and Blood Institute website.

2. National cardiovascular disease database. WHO India.3. Dalal PM, Parab PV. Cerebrovascular disease in type 2 diabetes mellitus. Neurol India. 2002;50(4):380-385 .

Summary

• Patients with diabetes require comprehensive evaluation for optimal management

• Guidelines recommend both lifestyle and pharmacotherapy for effective management

• Diabetic patients should be educated on their condition and the management

• The ADA recommends SMBG for monitoring glycaemic control• Diabetic patients require combination therapy at some point• Insulin therapy should be started without delay when required• The comorbidities associated with diabetes should be aggressively

managed

confluence module 2 new drs final version

Documents

diabetes care

established diabetes

diabetes mellitus

american diabetes association

diabetesrelated mortality

effective management

optimal management of

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