Approach to case of type 2 DM lifestyle modificatios indications to start drug therapy classification of antidiabetic drugs , mechanism of action , adeverse drug effects , doses , drug interactions , how to add differents class of drugs to give combination therapy . over view insulin therapy

1. Treatment of DM2
07-11-2023

2. Lesson plan
• Introduction – in short about role of Pancreas, Glucose metabolism
• Pharmacological therapies for DM, indications, CI, ADR and
Interaction- Based on presentation, severity, complication in a cost
effective therapy
Interaction: Q/A or doubts
Sum up & recapitulation
Formative assessment
Feedback both way
About next lesson

5. Classification of oral antidiabetic drugs

14. Organic cation transporter (OCT1 &2)

18. Peroxisome proliferator activator receptors (PPAR)

20. alpha glucosidase, Glucoamylase , Maltase ,Iso maltase ,Sucrase,
Acarbose ,Voglibose & Maglitol

24. Semaglutide
• Semaglutide is indicated as an adjunct to diet and exercise to
improve glycemic control in adults with type 2 diabetes.
• It can be administered by subcutaneous injection or taken orally.
• Semaglutide is a glucagon-like peptide-1 receptor agonist.

25. Semaglutide cont…
• The most common side effects include nausea, vomiting, diarrhea,
abdominal pain, and constipation.
• contraindicated in people with a personal or family history of medullary
thyroid carcinoma or with multiple endocrine neoplasia type 2
• Semaglutide's half-life in the blood is about seven days

28. Linagliptin
• Linagliptin is a dipeptidyl peptidase-4 inhibitor that works by increasing the
production of insulin and decreasing the production of glucagon by
the pancreas.
• Common side effects include inflammation of the nose and throat.
• Serious side effects may include angioedema, pancreatitis, joint pain.
• Use in pregnancy and breastfeeding is not recommended.
• Can be used safely in CKD

29. Sodium-glucose co-transporter 2 inhibitors

30. Mechanism of action SGLT2 inhibitor

31. Amylin analauge

32. Pramlintide –
• Pramlintide is a synthetic analog of human amylin that slows gastric
emptying, reduces postprandial rises in blood glucose concentrations, and
• modestly improves A1C concentrations in patients with type 1 and type 2
diabetes when injected subcutaneously three times per day

33. Pramlintide

34. Sum up Treatment of type2 DM

35. Treatment plan of type2 DM

36. Fig. 20.10 The recommended approach for the management of type 2 diabetes

37. Insulins

40. Types of Insulins for therapy
• Basal insulin
• Meal insulin

41. Basal insulin
• Intermediate –acting: NPH (Humulin N® , Insulatard® )
• Long-acting:
Glargine U-100 (Lantus® )
Glargine U-300 (Toujeo® )
Glargine biosimilar (Basaglar ®)
Detemir (Levemir ®)
Degludec (Tresiba® )
All look opaque (like milky water)

42. Meal Insulin
• Short-acting: Regular (Actrapid®, Humulin R®, Novolin R®)
• Rapid-acting: (analogs) –
Lispro (Humalog®) –
Aspart (Novorapid®, Novolog®) –
Glulisine (Apidra®)
• All look clear (like water)

43. Fig. 20.13 Amino acid structure of insulin and insulin analogues.
The areas in the
shaded colours show
the modifications
made to the normal
structure of insulin.
These are important in
altering the
pharmocokinetic
properties of the
analogues.

45. Animal Insulins

46. Short Comings on Animal Insulins
• Impurity
• Antigenicity
• Allergic reaction

47. Shortfalls of Regular Human Insulin (1978)
• Short acting in nature( 6-8 hours).
• Multiple daily injections to match physiological release
pattern.
• Less treatment satisfaction.
• Unpredictable Hypoglycemia

48. Concept of Basal Insulin
Neutral Protamine Hagedorn(NPH 1940-50)
• Hans Christian Hagedorn in 1936 added protamine from trout semen
to insulin.
• Protamine is a highly basic protein
• Later Zinc was added to stabilize the complex
• Leads to microprecipitation and delayed absorption and prolonged
duration of action
• 1950 Nordisk markets NPH Insulin

49. Rationality of Basal Insulin
• Basal insulin suppresses hepatic glucose output and also lipolysis
between meals and in night
• Prevents Ketoacidosis in Type 1
• Most individuals with type 2 diabetes will achieve adequate
glycemic control with the addition of basal insulin alone

54. Summary of Basal insulin
• long-acting insulin analogs (insulin glargine and insulin detemir) are
not superior to NPH insulin in efficacy terms as determined by the
number of participants reaching HbA1c targets.
• Compared with use of NPH insulin, the use of the standard long-
acting insulin analogs with relatively flat action profiles is associated
with up to a 50% reduced risk of nocturnal hypoglycemia.
• Basal insulin is now the cornerstone of insulin regime in Diabetes.
• It is convenient, effective ,less hypoglycemia

55. Summary of Basal insulin cont….
• Glargine for all practical purposes is the gold standard basal insulin.
• Frequent monitoring, patient education is also integral part.
• Proper injection technique should be taught.
• Basal insulin have to supplemented with prandial insulin in Type 1
DM and selected cases of Type T2 DM.
• In pregnancy, NPH and Detemir are recommended basal insulins.

56. Premixed insulins
• NPH/R 70/30
• Aspart 70/30
• Aspart 50/50
• Lispro 75/25
• Lispro 50/50
All premixed insulins look cloudy (like milky water)

57. Commonly used regimens:
• The different types of insulins can be given in
any different combination.
• Commonly used regimens:
• Once daily.
• Twice daily.
• Basal bolus.
• Three times per day regimen.
• Continuous s.c. insulin infusions (CSIIs).

58. Insulin activity profile with a once daily injection of
long-acting insulin. (Basal insulin)

60. Insulin activity profile with twice daily injection of
mixed (biphasic) insulin.

61. `

62. Insulin activity profile using a ‘basal bolus’ regimen.

64. Insulin activity profile using a CSII. (Continuous s.c. insulin
infusions).
Boluses can be adjusted to carbohydrate load of individual
meals.

68. Advantages of Insulin Therapy
• • Oldest of the currently available medications, has the most clinical
experience
• • Most effective of the diabetes medications in lowering glycemia –
Can decrease any level of elevated HbA1c – No maximum dose of
insulin beyond which a therapeutic effect will not occur
•
• • Beneficial effects on triglyceride and HDL cholesterol levels N

69. Disadvantages of Insulin Therapy
• • Weight gain ~ 2-4 kg – May adversely affect cardiovascular health
• • Hypoglycemia – However, rates of severe hypoglycemia in patients
with type 2 diabetes are low…
1.Type 1 DM: 61 events per 100 patient-years
2.Type 2 DM: 1-3 events per 100 patient-years

71. Fig. 20.16 Artificial pancreas.
The artificial pancreas (AP) can vary in its set up
and the different components employed in its
delivery but core to an AP system are:
(1) a continuous glucose monitor (CGM)
measuring interstitial glucose levels every
5–15 minutes;
(2) a smartphone (or personal glucose
monitor) with an app that uses the glucose
information from the CGM along with
modifications inserted by the user to
calculate how much insulin should be
delivered. This is communicated wirelessly
to
(3) the insulin pump that delivers insulin
subcutaneously as directed.

72. Transplanting islet cells.

73. Fig. 20.18 Transplanting islet cells.
(1)Pancreas obtained from
suitable human donor.
(2) Pancreatic islets containing
insulin-producing β cells are
isolated first in a Ricordi
chamber.
(3) Islets, once separated and
purified, are infused into the
hepatic portal vein.
(4) Once embedded in the liver,
pancreatic islets secrete insulin
in response to changes in portal
vein glucose.

74. Assessment

75. • Which amongst the following antidiabetic drugs has highest risk of
• hypoglycemia?
A. Linagliptin
B. Dapagliflozin
C. Glimepiride
D. Pioglitazone

76. • Mechanism action of metformin is:
A. Decreases hepatic glucose production
B. Increases insulin release
C. Increases renal glucose excretion
D. Increases lipogenesis

77. • Which of the following drug used in diabetes mellitus needs no dose
modification in CKD:
A. Metformin
B. Glimeperide
C. Linagliptin
D. Sitagliptin

80. Insulin vials
• “U-100 “ = every 1 ml has 100 units
• 1 vial has 10 ml = 1000 units
• New bottles should be kept in refrigerator [2-8 C°) [not freezer] until
expiration date
• Opened vials are valid for 4 weeks
• Opened vials can be kept in refrigerator or in room temperature (15-
25 C°)

81. Care of insulin vials
• Do not keep in hot places.
• Do not keep in a freezer.
• Do not leave in sunlight.
• Never use insulin if expired.
• Write the date on the insulin vial on the day you open it or start
keeping it outside the fridge.
• Throw the insulin away 4 weeks after opened or since kept out of the
fridge.

82. Care of insulin vials
• Inspect your insulin before each use.
• Look for changes in color or clarity.
• Look for clumps, solid white particles or crystals in the bottle or pen.
• Insulin that is clear should always be clear and never look cloudy.

83. What time to give insulin?
NPH: -
• At bedtime - Or
• usually twice/day (usually mixed with meal insulin)
Glargine/Detemir: -
• At bedtime (or AM) –
• Some need twice daily
Degludec: - Once daily (at same time of the day)

84. Indications for insulin
• Failure of non-insulin glucose-lowering therapy
• Type 1 DM
• Type of DM is not known
• Pregnancy
• Significant symptomatic hyperglycemia (random ≥ 300 mg)
or A1c ≥ 10
• In-hospital

85. What time to give insulin?
Regular:
• - 30 minutes before meals (once, twice or 3 times/day)
Rapid-acting insulins:
• - 5 minutes before meals (once, twice or 3 times/day)
• - Can be given immediately after meals

86. What time to give insulin?
Premixed 70/30 (Mixtard® 30 or Humulin® 70/30)
• - 30 minutes before meals (once, twice or 3 times/day)
Aspart 70/30, Lispro 75/25, Lispro 50/50:
• - 5 minutes before meals (once, twice or 3 times/day)

87. Which insulin to use?
Depends on:
Glucose control
Patient characteristics
Lifestyle
Patient preference

93. `

96. Management of diabetic patients
undergoing surgery and general anaesthesia.
(eGFR = estimated glomerular filtration rate; GLP-1 = glucagon-like peptide 1; IV = intravenous;
U&Es = urea and electrolytes)

98. Fig. 20.11 Time course of changes in HbA1cduring UKPDS
Fig. 20.11 Time course of changes in
HbA1c during the United Kingdom
Prospective Diabetes Study (UKPDS).
 In the UKPDS there was loss of
glycaemic control with time in patients
receiving monotherapy, independently
of their randomisation to conventional or
intensive glycaemic control, consistent
with progressive decline in β-cell
function
(see Fig. 20.8). Adapted from UK Prospective Diabetes Study Group. UKPDS 33. Lancet 1998; 352:837–
853

99. Fig. 20.10
• First-line drug treatment should be metformin.
• Second- and third-line treatment should be chosen based on the
efficacy, hypoglycaemia risk, weight effects and other side-effects,
and costs of the therapy in discussion with the patient.
• (DPP-4-i = dipeptidyl peptidase 4 inhibitor; fxs = fractures; GI = gastrointestinal; GLP-1-RA =
glucagon-like peptide 1 receptor agonist; GU = genitourinary; HF, heart failure; SGLT2-i = sodium
and glucose transporter 2 inhibitor; SU, sulphonylurea; TZD = thiazolidinedione) Adapted from the
American Diabetes Association/European Association for the Study of Diabetes joint position
statement, 2015. Diabetes Care 2015; 38:140–149

104. Sum up Anti DM type2 therapy

105. Fig. 20.10 The recommended approach for the management of type 2 diabetes