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Presentation By: PRATIKSHA V. DOKE
M.PHARM 1st year
Oriental college of pharmacy
Guided by: IMTIAZ ANSARI SIR
1
Diabetes mellitus (DM), commonly referred to as diabetes, is a group of
metabolic diseases in which there are high blood sugar levels over a prolonged
period. Diabetes is due to either the pancreas not producing enough insulin or the
cells of the body not responding properly to the insulin produced. There are three
main types of diabetes mellitus:
• Type 1 DM results from the pancreas's failure to produce enough insulin. This
form was previously referred to as "insulin-dependent diabetes mellitus" (IDDM)
or "juvenile diabetes". The cause is unknown.
• Type 2 DM begins with insulin resistance, a condition in which cells fail to
respond to insulin properly. As the disease progresses a lack of insulin may also
develop.This form was previously referred to as "non insulin-dependent diabetes
mellitus" (NIDDM) or "adult-onset diabetes". The primary cause is excessive body
weight and not enough exercise.
• GESTATIONAL DIABETES is the third main form and occurs when pregnant
women without a previous history of diabetes develop high blood-sugar levels.2
3
4
5
SIGN & SYMPTOMS
• The classic symptoms of untreated diabetes are:
1. weight loss,
2. polyuria (increased urination),
3. polydipsia (increased thirst), and
4. polyphagia (increased hunger)
6
7
8
Management
• SURGICAL
• DIETARY
• EXERCISE
• SELF MONITORING OF BLOOD GLUCOSE [SMBG]
• FOOT CARE
• HERBAL DRUG
• PHARMACOLOGICAL
9
Surgical management
1. Pancreas Transplant ( Not Usually Done)
2. Islet Cell Transplants
10
Dietary management
Goals
• Maintain near-normal blood glucose levels
• Achieve optimal serum lipid levels
• Provide adequate calories for reasonable weight
• Prevent & treat acute complications of insulin treated diabetes
• Improve overall health through optimal nutrition
11
Diet Composition
• Carbohydrates: 60 – 70% of daily diet
• Protein: 15 – 20% of daily diet
• Fats: No more than 10% of total calories from saturated fats
• Fibre: 20 to 35 grams/day; promotes intestinal motility and gives feeling of
fullness
• Sodium: recommended intake 1000 mg per 1000 kcal
• Sweeteners approved by FDA instead of refined sugars
• Limited use of alcohol: potential hypoglycaemic effect of insulin and oral
hypoglycaemic
12
Alcohol and Diabetes
Increase risk of…
• Hypoglycemia
• Affects the liver
• Don’t take on empty stomach
• Esp. if on insulin or oral hypoglycemic meds
13
Exercise
• Decreases blood glucose levels
• Increases the uptake of glucose by body muscle
• Potentiates action of insulin
• Decreases insulin requirement
• Effect lasts 24 hours
• Increases circulation
•Improve serum lipid levels
•Improves cardiovascular status
•Assist with wt control
•Decreases stress
14
Monitoring Glucose
• SMBG
• Glucometers
• Urine testing for glucose (2-4 times a day )
• Continuous glucose monitoring system
15
SELF MONITORING OF BLOOD GLUCOSE
(SMBG)
16
Foot care
17
18
HERBAL DRUGS
DRUGS SOURCE MOA
KARELA Fruit of Momardica
charantia
Family:Gutturbitaceae
Increase the insulin
secreation
FENUGREEK Seeds of Trigonella foenum
graecum
Family:Fabaceae
Reduced the glucose
absorption in blood
PHARMACOLOGICAL
 Insulin
 Sensitizers
• Biguanides
• Thiazolidinediones
 Secretagogues
• Sulfonylureas
• Nonsulfonylurea secretagogues
 Alpha-glucosidase inhibitors
 Peptide analogs
• Injectable Incretin mimetics
• Injectable Amylin analogues
 Glycosurics
19
INSULIN
20
DRUG MOA ADR MKD
FORMULATION
METFORMIN -decreases hepatic glucose production by
suppressing hepatic gluconeogenesis
-decreases intestinal absorption of glucose
-improving insulin sensitivity by increasing
peripheral glucose uptake and utilization
vomiting, diarrhea,
abdominal pain, tachycardia,
drowsiness, and, rarely,
hypoglycemia or
hyperglycemia
Actoplus Met
Janumet M1
PHENFORMIN BANNED DUE TO HIGHER RISK OF LACTIC ACIDOSIS
Sensitizers:
Insulin sensitizers address the core problem in Type II diabetes—insulin
resistance.
BISGUINIDES
21
THIAZOLIDINEDIONES
DRUG MOA ADR MKD FORMULATION
Rosiglitazone PPARɣ in fat tissue Plasma Volume
Expansion, Edema, Weight
Gain, Headache,
Myalgia And Mild Anaemia
Avandia
(GlaxoSmithKline)
Pioglitazone PPARɣ as well as PPARα Increase the chance of
pregnancy in individuals taking
oral contraception.
Glizone (Zydus Cadila)
Pioz
This novel class of oral antidiabetic drugs are selective agonists for the nuclear peroxisome
prolierator-activated receptors which enhances the transcription of several insulin responsive genes.
22
Secretagogues
Secretagogues are drugs that increase insulin output from the pancreas.
23
DRUG MOA ADR MKD FORMULATION
TOLBUTAMIDE
(1st GEN)
 Inhibit the ATP-potassium
channels (ie SULPHONYLUREA
RECEPTOR SUR-1 RECEPTOR) on
the beta cell membraneof
Pancreas.
 Decreases the efflux of potassium
 Depolarization of the cell
 Causing ca2+ influx
 Ca2+ -calmodulin complex
formation
 Exocytosis of insulin vesicles
leading to insulin release
Nausea, vomiting,
flatulence, diarrhoea or
constipation, headache,
paresthesias and weight
gain.
 The second generation
sulfonylureas are more
potent, can be
administered in lower
doses, and can be given
on a once daily basis
Rastinone
ACETOHEXAMIDE
(1st GEN)
Dymelor
Glipizide
(2nd GEN)
Glipizide XL
Glipizide ER
Glimepiride
(2nd GEN)
Amaryl
Gliclazide
(2nd GEN)
Diamicron
Gliclazide
SULFONYLUREAS
24
DRUG MOA ADR MKD FORMULATION
MEGLITINIDES  Same as Sulfonylureas
 But have less affinity for
SUR-1 Receptor
weight gain and
hypoglycemia
REPAGLINIDE Gluconorm 0.5mg
NATEGLINIDE Nateglinide
NON-SULFONYLUREAS
25
ALPHA-GLUCOSIDASE INHIBITORS
DRUG MOA ADR MKD FORMULATION
Miglitol  Reversible inhibition of membrane-
bound intestinal α-glucoside
hydrolase enzymes which hydrolyzes
oligosaccharides, trisaccharides, and
disaccharides to glucose.
 Less glucose is absorbed because
the carbohydrates are not broken
down into glucose molecules
Nausea, vomiting,
flatulence, diarrhoea
or constipation,
headache, weight
gain.
Glyset
Acarbose Glucobay
Voglibose Voglibose
Vobose
26
PEPTIDE ANALOGS
Injectable Incretin mimetics
27
DRUG MOA ADR MKD
FORMULATION
GLUCAGON-LIKE PEPTIDE-1
AGONIST(GLP-1 agonist)
Exenatide
 Enhance glucose-dependent insulin
secretion
 Suppresses pancreatic release of
glucagon which stop the liver from
overproducing sugar when it is
unneeded.
Bydureon
Byetta
Dipeptidyl Peptidase-4
Inhibitors (DPP-4 inhibitors)
VILDAGLIPTIN
SITAGLIPTIN
 Inhibits the inactivation of GLP-1and
GIP by DPP-4,
 Allowing GLP-1 and GIP to potentiate
the secretion of insulin in the beta cells
 Suppress glucagon release by the
pancreas.
Nausea,
Hypoglycemia,
Tremor,
Headache,
Dizziness
Jalra-M
Januvia
28
DRUG MOA ADR MKD FORMULATION
PRAMLINTIDE  Modulation of the rate of gastric
emptying,
 Prevention of post-prandial rise in
glucagon levels,
 By increasing sensations of satiety,
Weight loss Symlinpen
INJECTABLE AMYLIN ANALOGUES
29
GLYCOSURICS
DRUG MOA ADR MKD FORMULATION
DAPAGLIFLOZIN
EMPAGLIFLOZIN
CANAGLIFLOZIN
 SODIUM/GLUCOSE COTRANSPORTER
2 (SGLT2) is a member of the sodium
glucose cotransporter family which are
sodium-dependent glucose transport
proteins
 SGLT2 inhibitors lead to a reduction in
blood glucose levels.
Weight loss Farxiga
Jardiance
30
How Do Insulin Pumps Work?
Insulin pumps deliver insulin by continuous infusion through a single subcutaneous site
which is replaced, on average, every three days. Only rapid-acting insulin is used, and the
analogue insulin’s have gained popularity over regular insulin for this purpose . A pump
delivers programmable insulin dose around the clock which is tailored to the patient’s 24-
h glucose profile. The insulin requirements may be affected by the individual’s
physiology, the type and duration of daily activity, work schedule, exercise, illness,
concomitant medications, etc.
31
INSULIN PUMPS
• Insulin pens provide a compact and portable advantage for people with type 1
diabetes on multiple daily injections. Although they are easy to use, health care
providers unfamiliar with the pens may be hesitant to teach patients about
them. But once a patient has used a pen, he or she will not want to return to
using the traditional bottles and syringe . Pens provide increased ease of use,
accuracy, convenience, and less pain and fear of injections. Disadvantages are
storage issues and increased cost over the conventional method
32
INSULIN PENS
INHALABLE INSULIN
After conducting further studies, Mannkind submitted a
new application, and in June, 2014, the FDA approved
Afrezza for both Type I and Type II adult diabetics, with
a label restriction for patients having asthma, active
lung cancer or COPD. In 2014 Mannkind and Sanofi
agreed that Sanofi would take over manufacturing and
marketing of Afrezza
Inhalable insulin is a powdered form of insulin,
delivered with a nebulizer into the lungs where it is
absorbed
33
34
REFERENCE
 Walker, Donald (November 2007). "Similarity Determination and Case
Retrieval in an Intelligent Decision Support System for Diabetes
Management" (PDF). Retrieved 2 October 2009.
 Alexander, G Caleb; Sehgal NL; Moloney RM; Stafford RS (27 October 2008).
"National trends in treatment of type 2 diabetes mellitus, 1994-2007".
Archives of Internal Medicine. 168 (19): 2088–2094.
 American Diabetes Association, Standards of medical care in diabetes—2014,
Diabetes Care, 2014; 37(1): S14-S80.
35
36

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Advances and Management of Diabetes Mellitus

  • 1. Presentation By: PRATIKSHA V. DOKE M.PHARM 1st year Oriental college of pharmacy Guided by: IMTIAZ ANSARI SIR 1
  • 2. Diabetes mellitus (DM), commonly referred to as diabetes, is a group of metabolic diseases in which there are high blood sugar levels over a prolonged period. Diabetes is due to either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin produced. There are three main types of diabetes mellitus: • Type 1 DM results from the pancreas's failure to produce enough insulin. This form was previously referred to as "insulin-dependent diabetes mellitus" (IDDM) or "juvenile diabetes". The cause is unknown. • Type 2 DM begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses a lack of insulin may also develop.This form was previously referred to as "non insulin-dependent diabetes mellitus" (NIDDM) or "adult-onset diabetes". The primary cause is excessive body weight and not enough exercise. • GESTATIONAL DIABETES is the third main form and occurs when pregnant women without a previous history of diabetes develop high blood-sugar levels.2
  • 3. 3
  • 4. 4
  • 5. 5
  • 6. SIGN & SYMPTOMS • The classic symptoms of untreated diabetes are: 1. weight loss, 2. polyuria (increased urination), 3. polydipsia (increased thirst), and 4. polyphagia (increased hunger) 6
  • 7. 7
  • 8. 8
  • 9. Management • SURGICAL • DIETARY • EXERCISE • SELF MONITORING OF BLOOD GLUCOSE [SMBG] • FOOT CARE • HERBAL DRUG • PHARMACOLOGICAL 9
  • 10. Surgical management 1. Pancreas Transplant ( Not Usually Done) 2. Islet Cell Transplants 10
  • 11. Dietary management Goals • Maintain near-normal blood glucose levels • Achieve optimal serum lipid levels • Provide adequate calories for reasonable weight • Prevent & treat acute complications of insulin treated diabetes • Improve overall health through optimal nutrition 11
  • 12. Diet Composition • Carbohydrates: 60 – 70% of daily diet • Protein: 15 – 20% of daily diet • Fats: No more than 10% of total calories from saturated fats • Fibre: 20 to 35 grams/day; promotes intestinal motility and gives feeling of fullness • Sodium: recommended intake 1000 mg per 1000 kcal • Sweeteners approved by FDA instead of refined sugars • Limited use of alcohol: potential hypoglycaemic effect of insulin and oral hypoglycaemic 12
  • 13. Alcohol and Diabetes Increase risk of… • Hypoglycemia • Affects the liver • Don’t take on empty stomach • Esp. if on insulin or oral hypoglycemic meds 13
  • 14. Exercise • Decreases blood glucose levels • Increases the uptake of glucose by body muscle • Potentiates action of insulin • Decreases insulin requirement • Effect lasts 24 hours • Increases circulation •Improve serum lipid levels •Improves cardiovascular status •Assist with wt control •Decreases stress 14
  • 15. Monitoring Glucose • SMBG • Glucometers • Urine testing for glucose (2-4 times a day ) • Continuous glucose monitoring system 15
  • 16. SELF MONITORING OF BLOOD GLUCOSE (SMBG) 16
  • 18. 18 HERBAL DRUGS DRUGS SOURCE MOA KARELA Fruit of Momardica charantia Family:Gutturbitaceae Increase the insulin secreation FENUGREEK Seeds of Trigonella foenum graecum Family:Fabaceae Reduced the glucose absorption in blood
  • 19. PHARMACOLOGICAL  Insulin  Sensitizers • Biguanides • Thiazolidinediones  Secretagogues • Sulfonylureas • Nonsulfonylurea secretagogues  Alpha-glucosidase inhibitors  Peptide analogs • Injectable Incretin mimetics • Injectable Amylin analogues  Glycosurics 19
  • 21. DRUG MOA ADR MKD FORMULATION METFORMIN -decreases hepatic glucose production by suppressing hepatic gluconeogenesis -decreases intestinal absorption of glucose -improving insulin sensitivity by increasing peripheral glucose uptake and utilization vomiting, diarrhea, abdominal pain, tachycardia, drowsiness, and, rarely, hypoglycemia or hyperglycemia Actoplus Met Janumet M1 PHENFORMIN BANNED DUE TO HIGHER RISK OF LACTIC ACIDOSIS Sensitizers: Insulin sensitizers address the core problem in Type II diabetes—insulin resistance. BISGUINIDES 21
  • 22. THIAZOLIDINEDIONES DRUG MOA ADR MKD FORMULATION Rosiglitazone PPARɣ in fat tissue Plasma Volume Expansion, Edema, Weight Gain, Headache, Myalgia And Mild Anaemia Avandia (GlaxoSmithKline) Pioglitazone PPARɣ as well as PPARα Increase the chance of pregnancy in individuals taking oral contraception. Glizone (Zydus Cadila) Pioz This novel class of oral antidiabetic drugs are selective agonists for the nuclear peroxisome prolierator-activated receptors which enhances the transcription of several insulin responsive genes. 22
  • 23. Secretagogues Secretagogues are drugs that increase insulin output from the pancreas. 23
  • 24. DRUG MOA ADR MKD FORMULATION TOLBUTAMIDE (1st GEN)  Inhibit the ATP-potassium channels (ie SULPHONYLUREA RECEPTOR SUR-1 RECEPTOR) on the beta cell membraneof Pancreas.  Decreases the efflux of potassium  Depolarization of the cell  Causing ca2+ influx  Ca2+ -calmodulin complex formation  Exocytosis of insulin vesicles leading to insulin release Nausea, vomiting, flatulence, diarrhoea or constipation, headache, paresthesias and weight gain.  The second generation sulfonylureas are more potent, can be administered in lower doses, and can be given on a once daily basis Rastinone ACETOHEXAMIDE (1st GEN) Dymelor Glipizide (2nd GEN) Glipizide XL Glipizide ER Glimepiride (2nd GEN) Amaryl Gliclazide (2nd GEN) Diamicron Gliclazide SULFONYLUREAS 24
  • 25. DRUG MOA ADR MKD FORMULATION MEGLITINIDES  Same as Sulfonylureas  But have less affinity for SUR-1 Receptor weight gain and hypoglycemia REPAGLINIDE Gluconorm 0.5mg NATEGLINIDE Nateglinide NON-SULFONYLUREAS 25
  • 26. ALPHA-GLUCOSIDASE INHIBITORS DRUG MOA ADR MKD FORMULATION Miglitol  Reversible inhibition of membrane- bound intestinal α-glucoside hydrolase enzymes which hydrolyzes oligosaccharides, trisaccharides, and disaccharides to glucose.  Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules Nausea, vomiting, flatulence, diarrhoea or constipation, headache, weight gain. Glyset Acarbose Glucobay Voglibose Voglibose Vobose 26
  • 28. DRUG MOA ADR MKD FORMULATION GLUCAGON-LIKE PEPTIDE-1 AGONIST(GLP-1 agonist) Exenatide  Enhance glucose-dependent insulin secretion  Suppresses pancreatic release of glucagon which stop the liver from overproducing sugar when it is unneeded. Bydureon Byetta Dipeptidyl Peptidase-4 Inhibitors (DPP-4 inhibitors) VILDAGLIPTIN SITAGLIPTIN  Inhibits the inactivation of GLP-1and GIP by DPP-4,  Allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells  Suppress glucagon release by the pancreas. Nausea, Hypoglycemia, Tremor, Headache, Dizziness Jalra-M Januvia 28
  • 29. DRUG MOA ADR MKD FORMULATION PRAMLINTIDE  Modulation of the rate of gastric emptying,  Prevention of post-prandial rise in glucagon levels,  By increasing sensations of satiety, Weight loss Symlinpen INJECTABLE AMYLIN ANALOGUES 29
  • 30. GLYCOSURICS DRUG MOA ADR MKD FORMULATION DAPAGLIFLOZIN EMPAGLIFLOZIN CANAGLIFLOZIN  SODIUM/GLUCOSE COTRANSPORTER 2 (SGLT2) is a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins  SGLT2 inhibitors lead to a reduction in blood glucose levels. Weight loss Farxiga Jardiance 30
  • 31. How Do Insulin Pumps Work? Insulin pumps deliver insulin by continuous infusion through a single subcutaneous site which is replaced, on average, every three days. Only rapid-acting insulin is used, and the analogue insulin’s have gained popularity over regular insulin for this purpose . A pump delivers programmable insulin dose around the clock which is tailored to the patient’s 24- h glucose profile. The insulin requirements may be affected by the individual’s physiology, the type and duration of daily activity, work schedule, exercise, illness, concomitant medications, etc. 31 INSULIN PUMPS
  • 32. • Insulin pens provide a compact and portable advantage for people with type 1 diabetes on multiple daily injections. Although they are easy to use, health care providers unfamiliar with the pens may be hesitant to teach patients about them. But once a patient has used a pen, he or she will not want to return to using the traditional bottles and syringe . Pens provide increased ease of use, accuracy, convenience, and less pain and fear of injections. Disadvantages are storage issues and increased cost over the conventional method 32 INSULIN PENS
  • 33. INHALABLE INSULIN After conducting further studies, Mannkind submitted a new application, and in June, 2014, the FDA approved Afrezza for both Type I and Type II adult diabetics, with a label restriction for patients having asthma, active lung cancer or COPD. In 2014 Mannkind and Sanofi agreed that Sanofi would take over manufacturing and marketing of Afrezza Inhalable insulin is a powdered form of insulin, delivered with a nebulizer into the lungs where it is absorbed 33
  • 34. 34
  • 35. REFERENCE  Walker, Donald (November 2007). "Similarity Determination and Case Retrieval in an Intelligent Decision Support System for Diabetes Management" (PDF). Retrieved 2 October 2009.  Alexander, G Caleb; Sehgal NL; Moloney RM; Stafford RS (27 October 2008). "National trends in treatment of type 2 diabetes mellitus, 1994-2007". Archives of Internal Medicine. 168 (19): 2088–2094.  American Diabetes Association, Standards of medical care in diabetes—2014, Diabetes Care, 2014; 37(1): S14-S80. 35
  • 36. 36