Controlling blood sugar (glucose) levels is the major goal of diabetes treatment, in order to prevent complications of the disease. Type 1 diabetes is managed with insulin as well as dietary changes and exercise. Type 2 diabetes may be managed with non-insulin medications, insulin, weight reduction, or dietary changes. Medications for type 2 diabetes are designed to increase insulin output by the pancreas, decrease the amount of glucose released from the liver, increase the sensitivity (response) of cells to insulin, decrease the absorption of carbohydrates from the intestine, and slow emptying of the stomach, thereby delaying nutrient digestion and absorption in the small intestine.

1. Dr. Chavan P.R.
Pharm D
Diabetes treatment

2. TREATMENT
General approach
 Maintain normal glycemia
 Reduces the risk of microvascular disease
complications
 Management of traditional cardiovascular risk factors
(I.E., Smoking cessation, treatment of dyslipidemia,
intensive blood pressure control, antiplatelet therapy)
 Regular monitoring for complications;
 Dietary and exercise modifications;
 Appropriate self-monitoring of blood glucose (SMBG);
and
 Appropriate assessment of laboratory parameters.

3. NONPHARMACOLOGIC
THERAPY
 • Medical nutrition therapy for individuals with
type 1 dm,
 Maintain a healthy body weight.
 Balanced meals -moderate in carbohydrates and
low in saturated fat,
 Type 2 dm - caloric restriction for weight loss.

4.  Aerobic exercise can improve insulin resistance
and glycemic control and may reduce
cardiovascular risk factors, contribute to weight
loss or maintenance, and improve well-being.
 Exercise should be started slowly in previously
sedentary patients.
 Older patients and those with atherosclerotic
disease should have a cardiovascular evaluation
prior to beginning a substantial exercise program.

8. PHARMACOLOGIC THERAPY
Currently 6 classes of drugs
 Sulfonylureas- Glibenclamide, Glipizide
 Biguanides- metformin
 Meglitinide analogs- Repaglinide, Nateglinide
 Thaizolidinediones- Pioglitazone
 Αlpha glucosidase inhibitors - Acarbose
 Dipeptidyl Peptidase-IV Inhibitors- Sitagliptin,
Vildagliptin

9. Insulin
 Anabolic and anti-catabolic hormone
 Plays major role in Carbohydrate, Protein and Fat
metabolism
 Cleaved from Pro-insulin insulin

10. Characteristics
 Categorization on the basis of source, strength,
onset, duration of action, analogs etc.
 Analogs- amino acids in insulin modified to impart
particular physico-chemical and pharmacokinetic
advantages
 U-500 and U-100 common insulins available in
USA
 U-500 for larger doses and vice a versa

11. Sources
 Beef or pork sources
 Beef insulin- differs by 3 AA
 Pork insulin- differs by 1 AA
 Now a days- recombinant DNA technology
insulins are used
 When injected sc it is in hexameric form….gets
dissociated into monomers

12. Types
 Rapid acting (15-30 min)
e.g. Aspart, lispro
 Intermediate acting (2-4 hrs)
e.g. Lente
 Long acting (4-10 hrs)
e.g. Glargine
 Short-acting insulins (30–60 minutes )
e.g.Humulin R (regular),
Novolin R (regular)

13. Pharmakokinetics
 Depending factors-onset, peak, duration of action
 Absorption depends on- source of insulin,
concentration, additives (Zinc, protamine), blood
flow to the area, injection site.

14. Common sites of injection
 Abdominal fat
 Posterior upper arm,
 Lateral thigh area
 Superior buttocks area

15. Degradation
 In liver, muscle, kidneys
 Liver 20-50%
 Kidneys 15-20%
 Inhaled insulin
Efficacy
 Glycemic control

16. Adverse effects
 Hypoglycemia & weight gain are major adverse
effects
 Patient education plays an important role in
hypoglycemia.
 Symptoms of hypoglycemia-tachycardia,
sweating
 Initial symptoms are often neuro-glycopenic i.E.
Confusion, agitation, LOC and/or progression to
coma
 Driving, certain sports
 Treatment- glucagon/glucose IV
 Takes 10-15 min to raise blood glucose levels

17. Dosing & administration
 Type 1- 0.5-0.6 units/kg
 Honeymoon phase- 0.1-0.4 units/kg
 Type 2 higher doses may be required depending
upon IR

18. Storage
 Unopened insulin is recommended to be
refrigerated (36-46ºF)
 Because of Financial constraints pts may attempt
the use after expiration
 How to identify?
 Clumping, ppt, discoloration

19. standards
 Never freeze. (Frozen insulin should be thrown
away.)
 Never use insulin beyond the expiration date
stamped on the vial, pen, or cartridge that is
supplied from the drug manufacturer.
 Never expose insulin to direct heat or light.
 Inspect insulin prior to each use. Any insulin that
has clumps or solid white particles should not be
used.
 Insulin that is supposed to be clear should not
have any cloudy appearance.

20.  Check storage guidelines specific to the insulin
formulation. This is usually in the product
package insert.
 Unopened, not-in-use insulin should be stored in
a refrigerator at a temperature of 36-46º f.
 Opened, in-use insulin should be stored at room
temperature below 86º f.
 If receiving insulin through the mail, always
confirm that the insulin is going to be stored
under proper requirements.
 When storing pre-filled insulin syringes, store
them with the needle pointing up.

21. Insulin and Other Injectable
Preparations
 Regular insulin
– slow onset of action subcutaneously,
- requiring injection 30 minutes prior to meals to
achieve optimal postprandial glucose control and
- to prevent delayed postmeal hypoglycemia.

22.  Lispro, aspart, and glulisine insulins are analogs
that are more rapidly absorbed, peak faster, and
have shorter durations of action than regular
insulin.
 more convenient dosing within 10 minutes of
meals,
 produces better efficacy in lowering postprandial
blood glucose than regular insulin in type 1 DM,
and
 minimizes delayed postmeal hypoglycemia.

23.  Neutral protamine hagedorn (NPH) is
intermediate-acting.
 Variability in absorption, inconsistent preparation
by the patient, and inherent pharmacokinetic
differences may contribute to a labile glucose
response, nocturnal hypoglycemia, and fasting
hyperglycemia.
 Glargine and detemir are long-acting “peakless”
human insulin analogs that result in less
nocturnal hypoglycemia than NPH insulin when

24.  In type 1 DM, the average daily insulin
requirement is 0.5 to 0.6 units/kg.
 Requirements may fall to 0.1 to 0.4 units/kg in the
honeymoon phase.
 Higher doses (0.5 to 1 unit/kg) are warranted
during acute illness or ketosis.

25.  In type 2 DM, a dosage range - 0.7 to 2.5
units/kg.
 Hypoglycemia and weight gain are the most
common adverse effects of insulin.
 Treatment of hypoglycemia is as follows:
✓ Glucose (10 to 15 g) given orally is the
recommended treatment in conscious patients.
✓ Dextrose IV may be required in individuals who
have lost consciousness.
✓ Glucagon, 1 g intramuscular, is the treatment of
choice in unconscious patients when IV access
cannot be established.

26.  Exenatide is a synthetic analog of exendin-4, a 39-
amino acid peptide isolated from the saliva of the Gila
monster that enhances glucose dependent insulin
secretion and reduces hepatic glucose production.
 It also decreases appetite and slows gastric emptying,
which may reduce caloric intake and cause weight
loss.
 It significantly decreases postprandial glucose
excursions but has only a modest effect on FPG
values.
 Exenatide should be used as adjunctive therapy in
patients who have not achieved adequate glycemic
control despite treatment with metformin, a
sulfonylurea, and/or a thiazolidinedione.

27.  The average A1C reduction is approximately
0.9%.
 The most common adverse effects are nausea,
vomiting, and diarrhea.
 The initial dose is 5 mcg subcutaneously twice
daily, titrated to 10 mcg twice daily in 1 month if
needed and as tolerated.
 It should be injected 0 to 60 minutes before the
morning and evening meals.

28.  Pramlintide is a synthetic analog of amylin, a
neurohormone cosecreted from β -cells with
insulin.
 Pramlintide suppresses inappropriately high
postprandial glucagon secretion, reduces food
intake (which can cause weight loss), and slows
gastric emptying.
 The average A1C reduction is approximately
0.6%, but optimization of concurrent insulin
therapy may result in further A1C decreases.

29.  Adverse effects - nausea, vomiting, and anorexia.
 It does not cause hypoglycemia when used
alone, but it is indicated only in patients receiving
insulin, so hypoglycemia can occur.
 If a prandial insulin dose is used, it should be
reduced by 30% to 50% when pramlintide is
started to minimize severe hypoglycemic
reactions.

30.  In type 2 DM, the starting dose is 60 mcg
subcutaneously prior to major meals;
 the dose is titrated up to 120 mcg per dose as
tolerated and as warranted based on postprandial
plasma glucose levels.
 In type 1 DM, dosing starts at 15 mcg prior to
each meal, titrated up to a maximum of 60 mcg
prior to each meal if tolerated and warranted.

31. Sulphonylureas (MOA)
 Increase insulin secretion
 Bind to a receptor SUR
 Ca channel opening and influx of Ca ions
 Depolarization
 Exocytosis
 Decrease in hepatic glucose production

33. Classification
First generation-
 Tolbutamide, Cholpropamide
Second generation-
 Glibenclamide (Glyburide),
 Glipizide
 Gliclazide
 Glimepiride

34. P’kinetics
 Metabolized in liver by CYP450 2C9 enzyme
 Excreted through urine
 Dosage can be titrated every 1 to 2 weeks
 Dose reduction in elderly with renal /hepatic
impairement
Efficacy
 Equipotent doses of SU are equally effective
 A1C will fall by 1.5% to 2% with FPG reductions of 60
to 70 mg/dL (3.3 to 3.9 mmol/L).

35. Adverse effects
 Hypoglycemia
 Weight gain
 Skin rash
 Hemolytic anemia
 GI disturbances
 cholestasis
Patients At risk of hypoglycemia
 skip meals,
 exercise vigorously,
 loss of weight
 renal insufficiency or advanced liver disease

36. Hyponatremia
 Na levels <129 mEq/L
 Risk factors-
 Age (>60 yrs)
 Female gender
 Concomitant use of thiazide diuretics
 chlorpropamide ,tolbutamide.

37. Short acting insulin
secretogogues
 Acts in analogous way to SU
 Bind to SUR & other distinct receptors
 Closure of ATP dependant K channels
 Depolarization
 Insulin release
 Repaglinide- benzoic acid derivative
 Nateglinide- phenylalanine acetic acid derivative

39.  Insulin release is glucose dependent and
diminishes at low blood glucose concentrations.
 Hypoglycemic risk appears to be less with
meglitinides than with sulfonylureas.
 The average reduction in A1C is about 0.8% to
1%.
 They should be administered before each meal
(up to 30 minutes prior).
 If a meal is skipped, the medication should also
be skipped.

40.  Repaglinide (Prandin) is initiated at 0.5 to 2 mg
with a maximum dose of 4 mg per meal (up to
four meals per day or 16 mg/day).
 Nateglinide (Starlix) dosing is 120 mg three times
daily before each meal. The dose may be lowered
to 60 mg per meal in patients who are near goal
A1C when therapy is initiated.

41. P’kinetics
 Rapidly absorbed (0.5-1 hr)
 Short half life (1-1.5 hrs)
 Both metabolized in liver
Adverse effects
 Hypoglycemia
 Less as compared to SU
 Weight gain

42. Biguanides
 Metformin
 Enhances insulin
sensitivity of both
hepatic and peripheral
(muscle) tissues
 ↓A1C - 1.5% to 2%
 ↓FPG by 60 to 80
mg/dL
 ↓Plasma TG & LDL-
8% to 15%
 ↑HDL upto 2%
 No hypoglycemia lonely

43. ADRS
 Abdominal discomfort,
 Stomach upset,
 Diarrhea,
 Anorexia, and a metallic taste
 Lactic acidosis,
 Congestive heart failure, or conditions
predisposing to hypoxemia or inherent lactic
acidosis

44. Dose
 Metformin immediate-release 500 mg twice daily with
the largest meals and increased by 500 mg weekly
until glycemic goals or 2,000 mg/day is achieved.
Metformin 850 mg can be dosed once daily and then
increased every 1 to 2 weeks to a maximum of 850
mg three times daily (2,550 mg/day).
 Metformin extended-release (Glucophage XR) can be
initiated with 500 mg with the evening meal and
increased by 500 mg weekly to a maximum dose of
2,000 mg/day. Administration two to three times a day
may help minimize GI side effects and improve
glycemic control. The 750-mg tablets can be titrated
weekly to the maximum dose of 2,250 mg/day.

45. Thiazolidinediones
 Agonists for the receptors- PPAR-gamma
 Peroxisome proliferator activated receptor gamma
 Located in fat & vascular tissues
 Less concentration in muscles
 Enhance transcription of several insulin responsive
genes
 Tend to reverse IR
 Suppression of hepatic gluconeogenesis
 Activation of genes regulating FA metabolism and
lipogenesis

47. P’kinetics
 ½ life periods
 Pioglitazone-3-7 hrs
 Rosiglitazone- 3-4 hrs

48. Outcomes
 6 months therapy,
 A1C - 1.5%
 FPG levels by about 60 to 70 mg/dL
 Glycemic lowering effect- 3 to 4 months of
therapy
 Pioglitazone- decrease TG- 10-20%, NO LDL
 Rosiglitazone- 5-15% LDL rise

49.  dilutional anemia – no t/t
 Pioglitazone (Actos) is started at 15 mg once
daily. The maximum dose is 45 mg/day.
 Rosiglitazone (Avandia) is initiated with 2 to 4 mg
once daily. The maximum dose is 8 mg/day. A
dose of 4 mg twice daily can reduce A1C by 0.2%
to 0.3% more than a dose of 8 mg taken once
daily.

50. ADRS
 Hepatotoxicity
 Low Hb levels (2-4%)
 Edema (4-5%)
 Weight gain
 MI

51. Αlpha glucosidase inhibitors
 Final enzymes in the digestion of CH
 Slows down & decrease digestion and absorption
of polysaccharides and sucrose
 Competitive inhibit- maltase, isomaltase, sucrase,
glucoamylase in small intestine
 Delay in breakdown sucrose and complex CH
 PPBS not increased

52. EFFICACY
 40-50 mg/dL reduction in PPBS
 HbA1c levels reduction 0.3-1%

53. ADR
 GI disturbances
 Bloating (swelling due to fluid/gas)
 Diarrhoea
 Flatulance (accumulation of gases)
 Degradation of undigested CH by microflora
results in prodution of gases (CO2 & methane)
 Hypoglycemia
 Increased AST & ALT levels

54. Dipeptidyl Peptidase-iv Inhibitors
 prolong the half-life of an endogenously produced
glucagon-like peptide-1.
 reduce the inappropriately elevated glucagon
post prandially and stimulate glucose dependent
insulin secretion
 A1C - 0.7% to 1% at a dose of 100 mg/day.
 Mild hypoglycemia

56.  Sitagliptin (Januvia) is usually dosed at 100 mg
orally once daily.
 In patients with renal impairment, the daily dose
should be reduced to 50 mg (creatinine clearance
30–50 mL/min) or 25 mg (creatinine clearance
<30 mL/min).
 Vildagliptin was not approved in the United
States at the time of this writing (June 2008). The
usual dose is expected to be similar to Sitagliptin.

58. Complications
 Retinopathy
 Neuropathy
 Nephropathy

61. Retinopathy
 Examination by an ophthalmologist at least every
6 to 12 months.
 Early background retinopathy may reverse with
improved glycemic control.
 More advanced disease will not regress with
improved control and may actually worsen with
short-term improvements in glycemia.
 Laser photocoagulation has markedly improved
sight preservation in diabetic patients.

63. Neuropathy
 Type 2 DM
 Paresthesias, numbness, or pain
 Feet
 symptomatic and empiric
 low-dose tricyclic antidepressants,
anticonvulsants (e.g., gabapentin, pregabalin,
carbamazepine), duloxetine, venlafaxine, topical
capsaicin, and various analgesics, including
tramadol and nonsteroidal antiinflammatory
drugs.

64.  Gastroparesis
 Discontinuation of medications that slow gastric
motility
 Metoclopramide or erythromycin
 Orthostatic hypotension may require
mineralocorticoids or adrenergic agonists.

65.  Diabetic diarrhea –nocturnal
-10-14 days t/t
 Doxycycline or metronidazole
 Octreotide
 Erectile dysfunction- sildenafil, vardenafil, tadalafil

67. Nephropathy
 Also called as Diabetic Kidney Disease
 Glomeruli get damaged
 Leaking of proteins in urine
 Proteinurea
 Common in T1DM but more people are there of
T2DM
 Detection through urine tests
 Treatment- ACE inhibitors

68. Nephropathy
 Glucose and blood pressure control
 Angiotensin-converting enzyme inhibitors and
angiotensin receptor
 Diuretics are frequently necessary due to volume-
expanded states and are recommended second-
line therapy.

69. Peripheral Vascular Disease and
Foot Ulcers
 Claudication and nonhealing foot ulcers
 Smoking cessation, correction of dyslipidemia, and
antiplatelet therapy
 Pentoxifylline (Trental) or cilostazol (Pletal)
 Revascularization is successful in selected patients.
 Local debridement and appropriate footwear and foot
care are important in the early treatment of foot lesions.
Topical treatments may be beneficial in more advanced
lesions.

70. Coronary Heart Disease
 Treatment of dyslipidemia and hypertension,
smoking cessation, antiplatelet therapy
 The National Cholesterol Education Program
Adult Treatment Panel III guidelines

72.  Niacin or a fibrate- if triglycerides are 201 to 499
mg/dL
 The American Diabetes Association and the
National Kidney Foundation- blood pressure of
<130/80 mm Hg
 Angiotensin-converting enzyme inhibitors and
angiotensin receptor blockers
 b blockers, diuretics, calcium channel blockers