4. Magnitude of problem of DM
ā¢ Major health problem
ā¢ >10% of adult population affected
ā¢ On the increase due to unhealthy life-style
ā¢ About 50% may remain undiagnosed
ā¢ Majority remain uncontrolled
ā¢ Morbidity and mortality high
5. Continuedā¦.
ā¢ 40 million diabetes world wide
ā¢ 6.3 million in india
ā¢ 4.6 million deaths due to DM per year
ā¢ Every 8 sec 2 people develop diabetes and 1 die due to diabetes
6. Definition of DM
Non communicable metabolic disease characterised by
hyperglycemia resulting from defect in insulin
action, insulin secretion or both
This may lead to abnormalities of carbohydrate, protein
and fat metabolism with significant disturbance in water
and electrolyte homeostasis
7. Continuedā¦.
The chronic hyperglycemia of DM is associated with long term
damage, dysfunction and failure of various organs, especially the
eyes,kidneys,nerves,heart and blood vessels.
8. Management of DM
ā¢ Establishing the diagnosis of diabetes
ā¢ Initial evaluation
ā¢ Therapeutic measures
ā¢ Follow-up and monitoring
13. Oral Agents- General Principles
ā¢ Most agents produce > 75% effect with 50% of maximum dose
ā¢ Small dose of 2 agents- better effect than maximum dose of
single agent
ā¢ Combination of 2 agents with different mode of action may be
considered early
ā¢ Side effects dose related
16. Sulphonylureas
Mode of Action
ā¢ close K.ATP channels in Ī² cell plasma membrane
ā¢ Mainly Pancreatic : ļ insulin secretion
ā¢ Defect in early post prandial secretion not corrected
ā¢ Work only with pancreatic insulin reserve
17. SU. INDICATIONS
Non obese Type 2 Diabetes Mellitus
ā¢ Can be combined with
Metformin / Glitazones / Insulin
ā¢ Give before food
ā¢ Effective in obese also ā but ļ weight
18. SU
ā¢ Potency next only to insulin
ā¢ Protein bound- not removed by dialysis
ā¢ Avoid glibenclamide in RF(GFR- <50ml)
ā¢ May be avoided in elderly/old age
19. SU. Side effects + disadv.
ā¢ Hypoglycemia ā esp. Glibenclamide
more in elderly & Renal Failure ā avoid
ā¢ Weight gain
ā¢ ?blunts myocardial ischemic pre-conditioning
20. Non SU secretagogues- meglitinides
REPAGLINIDE + NATEGLINIDE
ā¢ Stimulate early meal media. insulin secretion
ā¢ ļÆ post prandial glucose
ā¢ Duration of action āshort
ā¢ Hypoglycemia + weight gain less than SU
ā¢ Needs frequent doses
24. METFORMIN - INDICATIONS
First line therapy in obese type 2 DM- especially
overweight/obese
Combination therapy - with
SU
glitazones
incretin modifiers
insulin
25. Metformin - advantages
ā¢ Extensive experience of efficacy & safety
ā¢ No weight gain ( weight neutral/decrease)
ā¢ No hypoglycemia
ā¢ Decrease CVD events
26. Metformin- side effects
ā¢ GI upset- abd. Pain , vomiting , diarrhoea
ā¢ Extreme tiredness- in some
ā¢ Lactic acidosis- very rare(0.1/1000pt years)
ā¢ Vit B12 malabsorbtion- in up to 30%
27. METFORMIN - CONTRAINDICATIONS
ā¢ Hepatic/ renal/ respiratory failure
ā¢ Acute cardiac failure (Stable CCF can be used)
ā¢ Acute medical conditions like sepsis/AMI/stroke
ā¢ Acute surgical (major surgery/trauma/burns)
ā¢ Acute & C/c. metabolic acidosis
ā¢ IV Radio contrast administration- stop before 48 hrs. Restart after
48 hrs.
29. Mode of Action
ā¢ 70% more effective than Metformin
ā¢ Primary site of action ā Adipose tissue
ā¢ Improve glycemic control
ā¢ Preserve ļ¢ cell function
ā¢ Activates nuclear transcription factor- PPAR Ī³
30. Glitazones and Lipids
ā¢ ļ HDL , ļÆ TGL (pioglitazone)
ā¢ Anti atherogenic effect
ā¢ Rosiglitazone - banned
ā¢ Pioglitazone ā recently banned in india
31. Glitazones ā Side Effects
ā¢ Fluid Retention, Oedema
ā¢ Precipitation of CHF
ā¢ ? Bladder cancer with pioglitazone
Monotherapy ā No hypoglycemia
32. Glitazones - indications
Type 2 DM ā all stages
1. Monotherapy
ā¢ Pioglitazone 7.5 to 30 mg daily
2. Combination with SU, Metformin
33. Glitazones - Cautions
ā¢ Avoid glitazones in overt / occult CHF
ā¢ Weight gain ā be cautious
ā¢ Obesity ā do not combine Insulin & Glitazone
35. Incretins
ā¢ In Type 2 DM- deficiency of GLP1- GLP1 inactivated by DPP-4 enzyme
ā¢ GLP1 receptor agonist
exenatide
liraglutide
ā¢ Expensive
ā¢ Multiple injection needed- not commonly used
37. ļ” GLUCOSIDASE INHIBITORS
ā¢ Acarbose and voglibose
ā¢ Inhibit ļ” Glucosidase ā an enzyme at brush border of small intestine
breaking down oligosaccharides to monosaccharides
ā¢ Slow intestinal digestion & absorbtion of CHO
ā¢ Damp postprandial hyperglycemia
ā¢ Due to CHO malabsorption ā abdominal bloating, flatus, gassy diarrhea
38. SGLT 2 Inhibitors
ā¢ Sodium glucose cotransport 2 inhibitor
ā¢ Also called gliflozins
ā¢ It inhibits reabsorption of glucose from the PCT
ā¢ It promotes the excretion of glucose in the urine ( glucosuria)
leads to UTI
42. ā¢ The American Diabetes Association/ European Association for the
Study of Diabetes consensus report āManagement of Hyperglycemia
in Type 2 Diabetes, 2018ā and the 2019 update recommend a patient-
centered approach to choosing appropriate pharmacologic treatment
of blood glucose. This includes consideration of efficacy and key
patient factors:
ā¢ 1) important comorbidities such as atherosclerotic cardiovascular
disease (ASCVD) and indicators of high ASCVD risk, chronic kidney
disease (CKD), and heart failure (HF)
43. ā¢ 2) hypoglycemia risk,
ā¢ 3) effects on body weight,
ā¢ 4) side effects,
ā¢ 5) cost, and
ā¢ 6) patient preferences.
44.
45.
46. ā¢ Metformin is the preferred initial pharmacologic agent for the
treatment of type 2 diabetes.
ā¢ Once initiated, metformin should be continued as long as it is
tolerated and not contraindicated; other agents, including insulin,
should be added to metformin.
ā¢ Early combination therapy can be considered in some patients at
treatment initiation to extend the time to treatment failure.
47. ā¢ The early introduction of insulin should be considered if there is
evidence of ongoing catabolism (weight loss), if symptoms of
hyperglycemia are present, or when A1C levels (>10% ) or blood
glucose levels (>300 mg/dL) are very high.
ā¢ A patient-centered approach should be used to guide the choice of
pharmacologic agents. Considerations include cardiovascular
comorbidities, hypoglycemia risk, impact on weight, cost, risk for side
effects, and patient preferences
48. ā¢ Among patients with type 2 diabetes who have established
atherosclerotic cardiovascular disease or indicators of high risk,
established kidney disease, or heart failure, a sodiumāglucose
cotransporter 2 inhibitor or glucagon-like peptide 1 receptor agonist
with demonstrated cardiovascular disease benefit is recommended as
part of the glucose-lowering regimen independent of A1C and in
consideration of patient-specific factors.
49. ā¢ In patients with type 2 diabetes who need greater glucose lowering
than can be obtained with oral agents, glucagon-like peptide 1
receptor agonists are preferred to insulin when possible.
ā¢ Intensification of treatment for patients with type 2 diabetes not
meeting treatment goals should not be delayed.
ā¢ The medication regimen and medication-taking behavior should be
reevaluated at regular intervals (every 3ā6months) and adjusted as
needed to incorporate specific factors that impact choice of
treatment
51. A1C in the diagnosis of DM
ā¢ Recommended by the international expert Committee * 2009
ā¢ ADA 2010 (non āpregnant adults)
ā¢ DM > 6.5% (2 times )
ā¢ Performed by a method certified by the NGSP (national glycohemoglobin
standardization program certified method)
52. Advantage of A1C over FPG,OGTT
ā¢ Convenience āno fasting needed
ā¢ Greater stability
ā¢ Less variation due to acute illness /stress
ā¢ Better index of overall glycaemic exposure and risk of long term
complications
53. A1C - disadvantages
ā¢ Higher cost
ā¢ Non availability in many centers
ā¢ Lack of properly standardized labs
ā¢ Unreliable
ā¢ Hemoglobinopathies
ā¢ Change in red cell turn over āhemolytic anemia
ā¢ Chronic malaria, major blood loss , blood transfusion
ā¢ Rapidly developing type 1 DM
54. Sensitivity of FPG,HbA1c & 2 hr OGTT
ā¢ 2 hour OGTT > FPG> A1C
ā¢ A1c 30 % less early diabetes detected compared to FPG > 126
ā¢ 2 hr OGTT value detects max. numbers
55. Recommendations
ā¢ Perform the A1C test at least two times a year in patients who are
meeting treatment goals (and who have stable glycemic control).
ā¢ Perform the A1C test quarterly in patients whose therapy has
changed or who are not meeting glycemic goals.
ā¢ Point-of-care testing for A1C provides the opportunity for more
timely treatment changes.
56.
57. A1C GOALS
ā¢ An A1C goal for many nonpregnant adults of < 7% (53 mmol/mol) is
appropriate.
ā¢ On the basis of provider judgement and patient preference,
achievement of lower A1C levels (such as ,6.5%) may be acceptable
if this can be achieved safely without significant hypoglycemia
or other adverse effects of treatment.
58. ā¢ Less stringent A1C goals (such as ,8% [64 mmol/mol]) may be
appropriate for patients with a history of severe hypoglycemia,
limited life expectancy, advanced microvascular or macrovascular
complications, extensive comorbid conditions, or long-standing diabetes
in whom the goal is difficult to achieve despite diabetes self management
education, appropriate glucose monitoring, and effective doses of multiple
glucose lowering agents including insulin
ā¢ . Reassess glycemic targets over time based on the criteria