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of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I.

Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

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Page 1: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues.

assist. prof. Svystun I.I.

Page 3: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 4: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Guidelines for glycaemic control in DM

IDF AACE (2011) ADA

HbA1c (%) <6.5 ≤6.5 <7.0

Fasting/preprandial glucose(mmol/L/ mg/dL)

<6.0 / <110 <6.0 / <110 3.9-7.2 / 70-130

2-h postprandial glucose(mmol/L/ mg/dL)

<7.8 / <140 <7.8 / <140 <10.0 / <180

Page 5: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Indexes Level of compensation

good sufficient insufficient Fasting glycaemia (mmol/l)

4,4 - 6,0 6,0- 7,8 > 7,8

2 hours after meals

4,4 – 8,0 8,0-10,0 > 10,0

Hb A1c (%) < 6,5 6,5 – 8 > 8 Cholesterol (mmol/l)

< 5,0 5,0 – 6,5 > 6,5

Triglycerides (mmol/l)

< 1,7 1,7 – 2,2 > 2,2

HDL (mmol/l) > 1,1 0,9 – 1,1 < 0,9 Body mass index (kg/m2)

males < 25 females < 24

25- 27 24- 26

> 27 > 26

Blood pressure < 130/80 < 160/95 > 160/95

Criteria of DM compensation

Page 6: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 7: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 8: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

DCCT A1C levels and the risk of complications in type 1 diabetes

Patients with type 1 diabetes (n=1,441) Adapted from DCCT. Diabetes 1995;44:968-43.

Page 9: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 10: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

UKPDS: Tight glycamic control prevents complications

Page 11: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 12: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

(A) Association of severe hypoglycemia with mortality in intensive and standard treatment groups in ACCORD replotted from Bonds et al. (2010).

(B) Association of severe hypoglycemia with mortality in intensive and standard treatment groups in ADVANCE replotted from Holman et al. (2009).

Page 13: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Treatment goal HbA1c

Dedov et al. Diabetes mellitus. 2011;4:6-17. © 2011,Diabetes Mellitus.

Age Young Middle Eldery and/or life expectancy <5 years

No complicationsNo risk of hypoglycemia

<6,5% < 7,0% <7,5%

Severe complications and /or risk of hypoglycemia

< 7,0% <7,5% < 8,0%

Page 14: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

An A1C ≤6.5% may be targeted in some patients with type 2 diabetes to further lower the risk of nephropathy and retinopathy but this must be balanced against the risk of hypoglycemia

Less stringent A1C targets (7.1%–8.5% in most cases) may be appropriate in patients with type 1 or type 2 diabetes with any of the following:a) Limited life expectancyb) High level of functional dependencyc) Extensive coronary artery disease at high risk of ischemic eventsd) Multiple comorbiditiese) History of recurrent severe hypoglycemiaf) Hypoglycemia unawarenessg) Longstanding diabetes for whom it is difficult to achieve an A1C ≤7.0% despite effective doses of multiple antihyperglycemic agents, including intensified basal-bolus insulin therapyADA: Executive Summary: Standards of Medical Care

in Diabetes—2012; Diabetes Care January 2012

Page 15: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Methods of treatment DM Education Exercise program. Diet. Oral hypoglycemic agents or insulin

(indications for each vary with the type of DM and severity of the disease).

Page 16: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Self - controlPhysician has to

educate: - techniques of insulin

administration and measurement of urine

and blood glucose level (if taking insulin)

Page 17: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Exercise Exercise: Before diabetic patients engage in exercise program,

they should consult with their healthcare provider because they need to have a complete history and physical examination

Exercise (total of about 30 minutes a day, at least 5 days a week) lowers blood sugar levels by improving cell uptake of glucose.

Page 18: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

The main principles of diet

Balanced diet (diet should include physiologic meal components: carbohydrate comprises 50 – 60 % of total calories, fat – 24 – 25 % and protein – 16 – 15 %).

Page 19: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

The main principles of diet.

Normal-calorie diet in patients with type 1 DM (35-50 kcal/kg of ideal weight (weight = height – 100)) and

low-calorie diet in obese persons (mostly in patients with type 2 DM (20 – 25 kcal/kg of ideal weight)). We try to decrease weight in obese patients on 1-2 kg/month by such diet.

Page 20: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Oral hypoglycemic agents. Inadequate control of hyperglycemia by the diet and

exercises interventions suggests the need for a good glucose-lowering agent.

Oral hypoglycemic agents are useful only in the chronic management of patients with type 2 DM.

The most commonly used are: 1. sulfonilureas, 2. biguanides, 3. alpha-glucosidase inhibitors, 4. non-sulfonylureas insulin stimulators (glinides), 5. thiazolidinediones (glitazones), 6. dipeptidyl peptidase IV (DPP-IV) inhibitors,7. glucagon-like peptide-1 (GLP-1) receptor agonist,8. analogue of amylin (pramlintide)

Page 21: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

2 nd generation drugs (mg) Dose Additional effects Glibenclamide (Maninil, Euglucan, Daonil, Glinil, Gilamat, Gliben, Glucoven)

1; 1,75; 3,5; 5

1-2 12-24

Gliquidone (Glurenorm, Beglicor)

30 30-120

8-12 Without hepato- and nephrotoxic effects, metabo-lism through the intestinum

Gliclazide (Diamicron, Diabeton, Predian, Glizid) Diabeton MR

80 30

80-320 30-120

8-12 24

Normalizes micro- circulation, blood aggregation

Glipizide (Minidiab, Glucontrol, Antidiab)

5 20 8-12

3 rd generation drugs (mg)

Glimepiride (Amaryl) 1-6 6 24

Commonly used sulfonylureas

Page 22: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Action of sulfonilureas1. Influence on the pancreatic gland: increasing of the β-cells sensitivity to the glucose

and as a result higher secretion of insulin; stimulation of the exocytosis of insulin by

insulocytes;2. Nonpancreatic influence: increasing number of the receptors to insulin; normalization of receptors’ sensitivity to insulin; increasing of glucose transportation inside muscle

cells; stimulation of glycogen synthesis; decreasing of glycogenolysis and

glyconeogenesis; decreasing of glucagon secretion and others.

Page 23: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 24: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Side effects of sulfonilureas hypoglycemia (hypoglycemic effect of

sulfonilureas will be the most obvious in 7 – 12 days from the beginning of the treatment);

allergy; influence on gastrointestinal tract (nausea and

others); leucopenia (decreasing of the quantity of white

blood cells); primary or secondary resistance; weight gain .

Page 25: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Contrandications to sulfanilureas usage type 1 DM; blood diseases; acute infections, acute coronary heart and

cerebral diseases; trauma; pregnant diabetics or lactation; III – IV stages of angiopathy (but Glurenorm

can be used in patients chronic renal failure, because of gastrointestinal tract excretion);

coma and precoma.

Page 26: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Commonly used biguanides

Name of drug Dose in 1 tabl.

Daily dose

Duration of

action (hours)

Metformin (Dianormet, Siofor, Metfogamma, Glucophage Forte)

0,25; 0,5; 0,85; 1,0

0,5-2,5

8-10 12-14

Buformin (Adebit) Buformin Retard was withdrawn from the market in some countries due to an elevated risk of causing lactic acidosis

0,05 0,17

0,1-0,2 0,17-0,34

8-10 12-14

Page 27: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Action of biguanides

Page 28: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Contraindications to biguanides usage

type 1 DM; heart and lung disease with their insufficiency

(chronic heart and lung failure); status with hypoxemia; acute and chronic liver and kidney diseases with

decreased function; pregnant diabetics, lactation; old age; alcoholism; coma and precoma.

Page 29: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Alpha-glucosidase inhibitors

Name of drug Dose in 1 tabl.

Daily dose

Duration of action(hour

s) Acarbosa (Glucobay, Glucor, Prandase, Precose)

0,05; 0,1 0,15-0,6 2,7-9,6

Miglitol 0,025; 0,05; 0,1

0,05-0,3 2-4

Guar Gum (Guarem)

5,0 (gra-nules)

15-30 -

Page 30: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Action of alpha-glucosidase inhibitors

inhibition of gastrointestinal tract absorption (block of α-glucozidase);

lowering of postprandial glucose level (postprandial “spikes” in blood glucose are increasingly implicated as a major cause of cardiovascular complications);

partly reducing fasting glucose levels by indirectly stimulating insulin secretion in patients who retain β-cell function (and acarbose has a protective effect on β-cells).

www.rushakoff.com

Page 31: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Contrandications to alpha-glucosidase inhibitors

type 1 DM; Chronic gastrointestinal disorders:

pancreatitis, colitis, hepatitis.

Side effects of alpha-glucosidase inhibitors

- flatulence, abdominal bloating, diarrhea.

Page 32: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Non-sulfanylureas insulin stimulators

Name of drug Dose in 1 tabl.

Daily dose

Duration of action (hours)

Repaglinid (Novonorm, Roglid) (meglitinide analogs)

0,001; 0,002; 0,003; 0,004

0,001-0,016

3 - 4

Nateglinid (Starlix) (D-Phenilalanine-derivative)

0,06; 0,12; 0,18

0,18-0,54

1,5 - 3

Page 33: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Action of non-sulfanylureas insulin stimulator.

Stimulation of insulin production at meal times;

very rapid absorbtion from the intestine and metabolism in the liver;

(plasma half-life is less than 1 hour).

Page 34: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Indications to non-sulfanylureas insulin stimulator.

- can be used in elderly with type 2 DM (due to short half-life) and in renal impairment (because it is metabolized in liver).

Contraindications to non-sulfanylureas insulin stimulator.

- as for the sulfanilureas

Side effects of non-sulfanylureas insulin stimulator.

- hypoglycemia, transient elevation of liver enzymes, rash and visual disturbances.

Page 35: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Commonly used thiazolidinediones

Name of drug Dose in 1 tabl.

Daily dose

Duration of action (hours)

Rosiglitazone (Avandia, Roglit, Rosinorm)

0,002; 0,004; 0,008

0,004-0,008

Pioglitazone (Actos, Pionorm)

0,015; 0,03; 0,045

0,015-0,03

Up to 24 hours

Page 36: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Action of thiazolidinediones

Page 37: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Contraindications to thiazolidinediones usage

Diabetic coma, precoma, ketoacidosis; Acute and chronic diseases of the liver; Heart failure; Pregnancy, lactation; Children, teenagers; Allergic reactions to the drug.

Page 38: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

GLP-1 Analogues Exenatide

Synthetic form of Exendin-4, derived from the

salivary secretions of the Gila monster lizard (Heloderma suspectum)

Liraglutide Novel long-acting analog obtained by acylation of

GLP-1 with fatty acid chain

Page 39: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

0 3 6 9 12

0

100000

200000

300000

400000

Time After Meal (h)

Pla

sma

Exe

nd

in-4

Co

nce

ntr

atio

n (

pg

/mL

)

Exendin-4 in the Gila Monster

♦Exendin-4 was originallyisolated from thesalivary secretions ofthe Gila monster

♦Exendin-4 wassubsequently found tocirculate as a meal-related peptide in this animal

Data from Young AA. Insulin Resistance and Insulin Resistance Syndrome 2002, 235-262

Page 40: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

GLP-1 Modes of Action in Man GLP-1 Modes of Action in Man

GLP-1 is secretedfrom the L-cells

in the jejunumand ileum • Stimulate insulin secretion only when

blood glucose concentration is elevated

• Suppresses glucagon secretion

• Slows gastric emptying

Long term effectsdemonstrated in animals…

• Increases beta-cell cell mass and maintains beta-cell efficiency

• Reduces food intake

Upon ingestion of food…Upon ingestion of food…

Drucker DJ. Curr Pharm Des 2001; 7:1399-1412Drucker DJ. Mol Endocrinol 2003; 17:161-171

Drucker DJ. Curr Pharm Des 2001; 7:1399-1412Drucker DJ. Mol Endocrinol 2003; 17:161-171

Page 41: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Structure of native GLP-1 and two GLP-1 analogues

97% homology to native GLP-1

53% homology to native GLP-1

Page 42: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Exenatide (Byetta)

♦ Pen prefill- one month’s supply♦ Given bid, 30-60 minutes prior to meal (250 cal)♦ Nausea experienced by almost all initially, typically

remits within days♦ Start at 5 mcg BID, then increase to 10 mcg BID after 1

month♦ Current indication: failing SFU, metformin, or both♦ Not FDA approved with insulin or monotherapy♦ Pancreatitis warning♦ Continue exenatide only if a person has a reduction in

HbA1c>1% and >3% of initial body weight in 6 months

Page 43: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

LIRAGLUTIDE 97% homologous with native human GLP-1 Half life of 11-15 hours Permitting once daily injection 1.2 and 1.8 mg/day Added to metformin, it reduces HbA1c by 1.5%

(p<0.01) Main side effects are nausea and vomiting

Page 44: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Inhibition of DPP-4 Increases Active GLP-1

GLP-1 (9-36)inactive

IntestinalGLP-1

release

Mixed meal

GLP-1 (7-36)active

DPP-4

Adapted from Rothenberg P, et al. Diabetes. 2000;49(suppl 1):A39.

DPP-4inhibitor

GLP-1 (7-36)active

Page 45: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Summary of DPP-4 Inhibition

• Increases fasting and postprandial GLP-1 levels• Reduces fasting and postprandial glycemia• Improves ß-cell function

– Increases insulin secretion, reduces proinsulin/insulin ratio– Increases beta-cell mass

• Inhibits glucagon secretion– Reduces hepatic glucose production

• Increases insulin sensitivity• Reduces postprandial lipemia• No effect on gastric emptying or body weight• Reduces HbA1c by ~1%• Is safe and tolerable in short term• In renal impairment, dose decreased by 50%

Page 46: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

SITAGLIPTIN

Licensed for use in T2DM at a dose of 100 mg once a day Can be added to metformin, a glitazone, a sulfonylurea

or a sulfonylurea+metformin, when current regime does not achieve glycemic control

HbA1c reduction of 0.5-1% Weight neutral and low risk of hypoglycemia Post prandial glucose also reduced (p<0.05) compared

to placebo Slightly higher rates of constipation, nasopharyngitis and

dizziness

Page 47: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

VILDAGLIPTIN

Licensed at a dose of 50 mg once or twice daily In T2DM as dual oral therapy Reduces HbA1c by 0.6-1.1% Reduces postprandial glucose Weight neutral and low risk of hypoglycemia Main side effects are headache,

nosopharyngitis, dizziness

Page 48: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

DPP-4 inhibitors

Continue DPP-4 inhibitor therapy only if there is a reduction of >0.5% HbA1c in 6 months

DPP-4 inhibitor is preferable to a Glitazone if further weight gain would cause significant problems

TZDs are contraindicated

Page 49: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Therapy Expected A1c (%) decrease with monotherapy

Lifestyle modifications 1.0-2.0

Metformin 1.5-2.0

Sulfonylurea 1.5-2.0

GLP-1 agonist 0.5-0.9

TZD 0.5-1.5

a-glucosidase inhibitor 0.3-1.0

Glinide 0.8-1.0

DPP-IV inhibitor 0.7-1.0

Pramlintide 0.4-0.5

Insulin unlimited

Page 50: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

ADA Algorithm for Management of DiabetesDiabetes Care. 2009, 32:193-203

At diagnosis:Lifestyle

+Metformin

Lifestyle+Metformin+

Pioglitazone(No hypoglycemia, edema,

CHF, bone loss)

Lifestyle+Metformin+

Sulfonylurea

Lifestyle+Metformin+

Intensive insulin

Lifestyle+Metformin+

Basal Insulin

Lifestyle+Metformin+

GLP1 (No hypoglycemia, wt loss,

Nausea/vomiting)

Lifestyle+Metformin+

Pioglitazone+

Sulfonylurea

Lifestyle+Metformin+

Basal Insulin

Tier 2: less well-validatedtherapies

Tier 1: Well-validated core therapies

Step 1Step 1 Step 2Step 2 Step 3Step 3

Amylin agonists, GlinidesDPP-4 inhibitors may be appropriate in selected

patients

*Useful when hypoglycemia is to be

avoided

2009

Page 51: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 52: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes

(EASD).

Inzucchi SE, Bergenstal RM, Buse JB, et al. Diabetes Care. 2012 Apr 19.

2012

Page 53: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

From the history of insulin

Banting1891 - 1941

Best1899 - 1978

Macleod1876 - 1935

Collip1893 - 1965

Page 54: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Indications for insulin therapy

1. All patients with type 1 DM.2. Some patients with type 2 DM: uncontrolled diabetes by diet or oral

hypoglycemic agents; ketoacidosis, coma; acute and chronic liver and kidneys disease with

decreased function; pregnancy and lactation; II – IV stages of angiopathy; infection diseases; acute heart and cerebral diseases; surgery.

Page 55: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

InsulinType+(Trade Name) Onset of Action Peak Duration Nursing Intervention

Rapid-acting (Clear)

Insulin Lispro (Humalog) Insulin Aspart (Novorapid)

Apidra (insulin glulisine)

10-15min 60-90min 4-5hrs Take within 15 min before meals or within 20 min after meals

Short Acting/Regular Insulin (clear)

Humulin R

30-60 2-4hrs 5-8hrs Take 30 min before meals

Intermediate-acting (cloudy)

(NPH/Lente)

1-4hrs 4-12hrs 18-24hrs

Ultra Lente and Glargine

(clear)

4-8hrs 18hrs 24-38hrs Note: Glargine can not be mixed with any other insulin

Premixed: 10/90, 20/80, 30/70, 40/60, 50/50(cloudy)

ideal time to give patients with their premixed is

30 min before their meal, with their meal and after their meal

Drawing up Insulin: Clear then cloudy to avoid contaminating the clear insulin

Page 56: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Insulin preparations of ultrashort action(human analog, recombinant)

Insulin action

beginning maximum duration

NovoRapid (Insulin aspart) Novo-Nordisk

2-10 min 40 - 50 min 3 - 5 h

Humalog (insulin lispro)Lilly

Apidra (insulin glulisine)

Page 57: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Insulin preparations of short actionInsulin action

beginning maximum duration

Humodar R 100 Indar - human insulin (semi-synthetic)

30 min 1 - 3 h 5 - 8 hHumodar R 100 R Indar - human insulin (recombinant)

Farmasulin H (regular insulin human injection, [rDNA origin])

Farmak

Actrapid (НМ)

Novo-Nordisk

Humulin R (regular insulin human injection, [rDNA origin]),

Lilly

Insuman rapid (regular insulin human injection, [rDNA origin])

Sanofi-aventis

Page 58: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Insulin preparations of intermediate action

Insulin actionbeginning maximum duration

Humodar B 100 R Indar

1 – 1,5 h 6 - 8 h 12 – 18 h

Farmasulin Н NР Farmak

Protaphan (МС, НМ)

Novo-Nordisk

Insuman basal Aventis

Humulin NPH Lilly

Monotard НМ Novo-Nordisk

Page 59: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Insulin preparations of long action

Insulin actionbeginning maximum duration

Farmasulin Н L Farmak

3 – 4 h 10 -12 h 24 – 30 h

Ultralente Humulin Lilly

Ultratard НМ

Glargine (Lantus)Aventis

-(human analog, recombinant)

24 hDetemir (Levemir) Novo Nordisk

Page 60: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Insuman comb 25/75

Aventis 30 min 1,5-2 h 12-18 h

Humodar C15 Indar 30-45 min

1,5-3 h 12-18 h

Humodar C25 Indar 30-45 min

1,5-3 h 12-18 h

Humodar C50 Indar 30 min 1-3 h 6-10 h NovoMix® 30 Novo-

Nordisc 30 min 2-8 h 24 h

Insulin preparationscombined

Page 61: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 62: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Storing and Handling Insulin

Opened bottles stored at room temperature (15 to 30°C).

If stored in a refrigerator, unopened bottles are good until the expiration date printed on the bottle.

Opened bottles that are stored in a refrigerator should be used within one month of being opened.

Protect your insulin (bottles, pens, and cartridges) from extremes of hot and cold.

Never store your insulin in the freezer - once insulin is frozen, it loses its potency.

Page 63: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Initiation and modification of insulin therapy

It is started as soon as possible in an attempt to “rest” the damaged islet cells and help to “induce” a remission (“honeymoon” phase).

1 Unite

It is activity of 0,04082 mg of crystalic insulin (standart)

Page 64: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Initiation and modification of insulin therapy

We can use traditional or multiple component insulin program. The last is better.

Advantages include the following: hypoglycemic reactions may be decreased or

prevented because smaller doses of insulin are needed;

more physiologic match of insulin to meals is achieved.

Page 65: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Initiation and modification of insulin therapy to achieve diabetic control.Step 1: Estimate Total Daily Insulin (TDI) The daily insulin requirement in patients:- on the first year of the disease is 0,3 – 0,5

unite of insulin per kilogram of body weight (0,5 – if the patient with ketosis or DKA);

- on the next years is 0,6 – 0,8 – 1,0 unite/ kg of body weight.

Page 66: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Secretion of insulin in health people

Con

cen

trat

ion

of

insu

lin

3 Breakfast 2, Meal secretion 3 Lunch Dinner 1,5 1 0,5 7.00 12.00 19.00 24.00 7.00 0

Basal secretion

Page 67: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Initiation and modification of insulin therapy

2/3 of the total daily dose we give before breakfast, 1/3 in the evening and then make correction due to the glucose blood level. Insulin doses should be given 30 minutes before meals to allow for adequate absorption of regular insulin.

It using three or four shots of short-acting insulin (1/3 of total daily dose) plus intermediate-acting (2/3 of total daily dose) insulin daily twice a day.

Page 68: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

2/3 TDI

1/3 TDI

Page 69: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 70: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Treatment of type 2 DM

Page 71: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

NPH-Based Multiple-Dose Insulin Therapy (MDI)

2 injections: • Premix 70/30 before AM and evening meal OR NPH + R/aspart/lispro/glulisine (ratio 2:1)

before AM and evening meal; mix insulins in same syringe.

Starting Dose: 0.3-0.5 units/kg/day divided as follows: 2/3 morning, 1/3 evening; before meals

Page 72: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 73: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 74: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 75: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Methods of delivery insulin

Intravenous (IV) Syringes (SC) Pens Jet injectors Insulin pumps

Page 76: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 77: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Site Selection for the Injections

4 major areas: Arms-posterior surface Abdomen-avoid 1 inch

area around navel Thighs-anterior surface HipsNote: Systematic rotation of injection sites

within an anatomic area to prevent lipodystrophy.

Administering each injection 0.5-1inch away from the previous injection.

Page 78: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Some peculiarities of insulin therapy:

insulin acts faster when is administrated i/v;

subcutaneous and intramuscular absorption of insulin is decreased in the dehydrated or hypotensive patients;

the most rapid absorption from the abdomen;

exercise accelerates insulin absorption (before planned exercise program patient has to decrease insulin dose or take more caloric diet).

Page 79: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I
Page 80: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Side effects (complications) of insulin therapy.1. Hypoglycemia. - This complication represents insulin excess and it

can occur at any time (frequently at night (common symptom: early-morning headache)).

- Precipitating factors: irregular ingesting of food; extreme activity; alcohol ingestion; drug interaction; liver or renal disease; hypopituitarism; adrenal insufficiency.

Page 81: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Side effects (complications) of insulin therapy.

1. Hypoglycemia

It is a syndrome characterized by symptoms of sympathetic nervous system stimulation or central nervous system dysfunction that are provoked by an abnormally low plasma glucose level.

Hypoglycemia represents insulin excess and it can occur at any time.

Page 82: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Side effects (complications) of insulin therapy2. Somogyi effect (Somogyi phenomenon,

rebound effect). It is caused by overinsulinization: hyperglycemia

proceeded by insulin – induced hypoglycemia. Hypoglycemia causes an increase in the secretion of the counterregulatory hormones (glucagon, epinephrine, cortisol, growth hormone), which inhibit insulin secretion and increase glucose output by the liver (as a result of the stimulation of glucogenolysis and glucogenesis).

Treatment: gradual reduction of insulin dose.

Page 83: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Side effects (complications) of insulin therapy3. Dawn phenomenon. Many patients with type 1 DM demonstrate an

early morning (4 – 8 a.m.) rise in glucose levels, because of activation of counterregulatory hormones. It may be confused with the Somogyi phenomenon. Sampling of glucose levels throughout the night might help differentiate the two conditions.

Treatment: some have recommended an earlier injection in the morning (5 – 6 a.m.), and most suggest a late evening (before bedtime) injection of intermediate-acting insulin.

Page 84: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Side effects (complications) of insulin therapy

4. Allergic reactions.

These include burning and itching at the site of insulin injection; skin rash; vasculaties; purpura and anaphylactic reaction.

Treatment:

- antihistamines;

- changing of standard insulin to pure pork insulin or to human insulin;

- in extreme cases – glucocorticoids.

Page 85: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Side effects (complications) of insulin therapy5. Insulin resistance. - Clinical status characterized by insulin

resistance: obesity; therapy with oral contraceptives; glucocorticoid therapy; acromegaly; Cushing’s syndrome; acanthosis nigricans; chronic liver or renal disease. - Non-true insulin resistance may be caused by

long-time injections of insulin into the one site.

Page 86: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Side effects (complications) of insulin therapy

6. Lipodystrophy.

- It is atrophy or hypertrophy of the adipose tissue, which occur at the site of insulin injection.

- Treatment: changing the site of injection; the usage of human insulin.

Page 87: Novel methods of treatment of diabetic patients. Oral hypoglycemic agents, modern insulin preparations and its analogues. assist. prof. Svystun I.I

Thank you for

attention!