ALHA-GLUCOSIDASE INHIBITOR

ALHA-GLUCOSIDASE INHIBITOR

Acarbose

ALHA-GLUCOSIDASE INHIBITOR

Acarbose

• used 2-3 times daily after 1st bite of eat

  • Should not be used by px with renal problem

Acarbose

• Fermentation of carbohydrates into short chain fatty acids, releasing gas may cause flatulence, diarrhea and abdominal pain

Acarbose

May cause hypoglycemia when taken with sulfonylurea

glucose (dextrose) not sucrose

Acarbose

May cause hypoglycemia when taken with sulfonylurea

Tx

GLP-1

• rapidly degraded by dipeptidyl peptidase 4 (DPP-4) and by other enzymes such as endopeptidase 24.11

Exenatide

Liraglutide (Saxenda)

Albiglutide

Dulaglutide

GLUCAGON LIKE PETIDE-1 (GLP1) RECEPTOR AGONIST

Dulaglutide

• consists of two GLP-1 analog molecules covalently linked to an Fc fragment of human IgG4

• Dose: SQ 0.75 mg weekly

Albiglutide

• human GLP-1 dimer fused to human albumin.

• T1/2: 5 days; once weekly administration

Albiglutide

Lesser weightloss than liragutide and exenatide

Liraglutide (Saxenda)

• a soluble fatty acid-acylated GLP-1 analog

• T1/2: 12 hrs, OD dosing

Liraglutide (Saxenda)

dose of 3 mg daily has been approved for weight loss.

Exenatide

Fixed dose pen, administered 1 hr before breakfast and dinner

Exenatide

has a 53% homology with native GLP-1 and a glycine substitution to reduce degradation by DPP-4.

Exenatide

derivative of the exendin-4 peptide in Gila monster venom

Increased risk of pancreatitis

• Renal impairment with exenatide

• Should not be used in px with history and family history of medullary thyroid cancer or multiple endocrine neoplasia (MEN) syndrome type 2

ADR OF GLP1 RECEPTOR AGONIST

Sitagliptin

Saxagliptin

Linagliptin

Alogliptin

Vildagliptin (Galvus)

DIPEPTIDYL PEPTIDASE 4 (DDP-4) INHIBITORS

Vildagliptin (Galvus)

• (not available in the United States) lowers HbA1c levels by 0.5-1% when added to the therapeutic regimen of patients with type 2 diabetes

• Dose: 50mg once or twice daily

hepatitis

• Vildagliptin (Galvus)

• Rarely, it may cause

Alogliptin

lowers HbA1c by about 0.5-0.6% when added to metformin, sulfonylurea, or pioglitazone.

Alogliptin

• Dose: 25 mg orally daily.

• Renal impairment required dosage adjustment

• Do not give in px with liver failure

The risk of pancreatitis may be increased.

Linagliptin

ADR

Linagliptin

Biliary secretion, no dosage adjustment is needed in renal failure

Linagliptin

• lowers HbA1c by 0.4-0.6% when added to metformin, sulfonylurea, or pioglitazone.

• Dose: 5 mg daily orally

Saxagliptin

Renal impairment or CYP3A4 inhibitor meds require dosage adjustment

Saxagliptin

• Dose: Oral, 2.5-5 mg daily

• may increase the risk of heart failure

Sitagliptin

ADR: nasopharyngitis, URTI, headache,.hypoglycemia when combined with insulin, pancreatitis

Sitagliptin

• 100mg OD

• T1/2 of 12 hours

• Monotherapy or combined with metformin, sulfonylureas or thiazolidinediones

Sitagliptin

Monotherapy or combined with metformin, sulfonylureas or thiazolidinediones

Sodium-glucose transporter 2 (SGLT2)

• accounts for 90% of glucose reabsorption, and its inhibition causes glycosuria and lowers glucose levels in patients with type 2 diabetes.

Canagliflozin

Dapagliflozin (Farxiga)

Empagliflozin

SODIUM - GLUCOSE CO TRANSPORTER 2 INHIBITOR 

diabetic ketoacidosis

have been reported with off-label use of SGLT2 inhibitors in patients with type 1 diabetes

chronic kidney disease

As might be expected, the efficacy of the SGLT2 inhibitors is reduced in

canagliflozin and empagliflozin

C/I in GFR <45ml/min

Dapagliflozin

C/I in GFR <60ml/min

Empagliflozin

• reduces HbA1c by 0.5-0.7% when used alone or in combination with other oral agents or insulin

Empagliflozin

• modest weight loss of 2-3 kg.

• Dose: 10mg/ day

Dapagliflozin (Farxiga)

Dose: 10 mg daily; 5mg in px with liver failure

Dapagliflozin (Farxiga)

reduces HbA1c by 0.5-0.8% when used alone or in combination with other oral agents or insulin

Canagliflozin

• Dose: 100mg/ day

• reduce HbA by 0.6-1% when used alone or in combination with other oral agents or insulin

• Weight loss of 2 -5 kg

Pramlintide

an islet amyloid polypeptide (IAPP, amylin) analog.

Pramlintide

IAPP is a 37-amino-acid peptide present in insulin secretory granules and secreted with insulin

Pramlintide

IAPP reduces glucagon secretion, slows gastric emptying by a vagally mediated mechanism, and centrally decreases appetite.

Colesevelam hydrochloride,

the bile acid sequestrant and cholesterol-lowering drug, is approved as an antihyperglycemic therapy for persons with.Type 2 diabetes who are taking other medications or have not achieved adequate control with diet and exercise

Colesevelam hydrochloride,

• interruption of the enterohepatic circulation and a decrease in farnesoid X receptor (FXR) activation.

FXR

a nuclear receptor with multiple effects on cholesterol, glucose, and bile acid metabolism.

TYPE 1 DM

• Combination of rapid and long acting

• total daily insulin requirement in units is equal to the weight in pounds divided by four, or 0.55 times the person’s weight in kilograms.

TYPE 1 DM

3 or 4 insulin injections a day are necessary for safe and effective control of glucose levels.

TYPE 2 DM 

Normalization of glucose levels can occur with weight loss and improved insulin sensitivity in the obese patient with type 2 diabetes

• Short acting secretagogue before meal

• Px with hyperglycemia after carb-rich meals:

  • Give

Pioglitazone

Px with severe insulin resistance

GLP1 receptor agonist, DPP-4 inhibitor, SGLT2 inhibitor

Px concerned with weight gain

Metformin

has been shown to be.effective when combined with insulin therapy and should be continued.

HYPOGLYCEMIA

• Symptoms: tachycardia, palpitations, sweating, tremulousness) and parasympathetic (nausea, hunger) - and may progress to convulsions and coma if untreated

20-50 ml 50% glucose (D50%) IV bolus.for emergency, in case of loss of consciousness

HYPOGLYCEMIA

tx

DIABETIC KETOACIDOSIS

• a life-threatening medical emergency caused by inadequate or absent insulin replacement, which occurs in people with.type 1 diabetes and infrequently in those with type 2 diabetes.

DIABETIC KETOACIDOSIS

• Signs and symptoms

  • include nausea, vomiting, abdominal.pain,

  • deep slow (Kussmaul) breathing, change in mental status (including coma), elevated blood and urinary ketones and glucose,

DIABETIC KETOACIDOSIS

an arterial blood pH lower than 7.3, and low bicarbonate (15 mmol/L)

• TREATMENT

  • aggressive intravenous hydration and insulin therapy and maintenance of potassium and other electrolyte levels.

  • Fluid therapy generally begins with normal saline.

  • Regular human insulin should be used for intravenous therapy

    • starting dosage of about 0.1 U/kg/h.

DIABETIC KETOACIDOSIS

HYPEROSMOLAR HYPERGLYCEMIC SYNDROME

• profound hyperglycemia and dehydration. It is associated with.inadequate oral hydration,

• may drug induced dehydration caused by:

Kapag nag phenytoin, steroids, diuretics, and calcium channel blockers; and with peritoneal dialysis and hemodialysis

HYPEROSMOLAR HYPERGLYCEMIC SYNDROME

• Diagnosis

  • Seizure

  • Declining mental status

  • Plasma glucose of >600mg/dL

  • Persons with HHS are not acidotic unless DKA is also present.

• Diabetic necropathy (destruction in kidney)

• Diabetic neuropathy 

• Diabetic retinopathy (eye)

• Hypertension, Myocardial infarction  

• ESRD

• Blindness

• Autonomic and peripheral neuropathy

• MI

• Stroke

CHRONIC COMPLICATIONS OF DIABETES

Cigarette use

adds significantly to the risk of both microvascular and macrovascular complications in diabetic patients.