Alogliptin

Type I Diabetes Mellitus
Congestive Heart Failure
Prior history of malignancy
1. Due to increased risk of cancer invasion and metastases

See DPP-4 Inhibitor
Dipeptidyl Peptidase-4 (DPP-4) is an enzyme that degrades the Incretins GLP-1 and GLP-2
1. Incretins (GIP and GLP1) are normally released from GI Tract (enteroendocrine cells) following meals
2. Incretins increase Glucose dependent Insulin secretion, and inhibit Glucagon secretion
DPP4 Inhibitor Activity
1. DPP-4 Inhibitors block Incretin degradation
  1. Allows accumulation of GLP-1 by 2-3 fold
2. Activate Glucose-Dependent Insulinotropic Polypeptides
  1. Stimulates beta cells to secrete Insulin
  2. Lowers Blood Sugar, but low risk of Hypoglycemia
Differs from GLP1 Agonists
1. Weight neutral
2. No Nausea

DPP-4 Inhibitors are less than half as effective as lower cost medications (e.g. Metformin, Sulfonylureas)
No longterm evidence of improved outcomes
Decrease dose in renal Impairment
May consider for those close to goal AND
1. Already either on other Oral Hypoglycemics or in whom they are contraindicated (e.g. Chronic Kidney Disease)

Alogliptin (Nesina)
1. Tablets 6.25, 12.5 or 25 mg
2. First Gliptin to be generic (as of 2016)
Combinations
1. Kanzano (Alogliptin and Metformin)
2. Oseni (Alogliptin and Pioglitazone)

Alogliptin 25 mg orally daily
Renal Dosing
1. Creatinine Clearance 30 to 59 ml/min: 12.5 mg orally daily
2. Creatinine Clearance <30 ml/min: 6.25 mg orally daily

Unless otherwise noted, adverse effects are for DPP-4 Inhibitor in general
Acute Pancreatitis
1. Incidence may be as high as 1 in 50 for two years
2. Singh (2013) JAMA Intern Med 173(7):534-9 [PubMed]
Serious Allergic Reaction (Sitagliptin)
1. Anaphylaxis
2. Angioedema
Hepatotoxicity (Alogliptin, Vlidagliptin)
Headache
Bullous Pemphigoid
Congestive Heart Failure exacerbation
1. Risk of hospitalized CHF exacerbation: 1 in 150 patients/2 years using Saxigliptin or Alogliptin
2. Higher risk with pre-existing CHF and renal Impairment
3. Sitagliptin (Januvia) is less associated with CHF exacerbation
4. Scirica (2013) N Engl J Med 369(14):1317-26 [PubMed]
Severe, persistent Joint Pain (rare)
1. Stop agent if suspect Gliptin-induced pain (and avoid other Gliptins)
2. Consider other possible causes (e.g. Statin induced Myopathy)
3. FDA Alert
  1. http://www.fda.gov/drugs/drugsafety/ucm459579.htm

No longterm cardiovascular benefit (DPP-4 Inhibitor in general)
Lowers HBA1C 0.5 to 0.9% with a mean 0.6% (DPP-4 Inhibitor in general)
1. Contrast with Metformin, Sulfonylureas, GLP-1 Agonists, Pioglitazone lower A1C 1.0 to 1.5% at generic costs
2. When combined with other hypoglycemics, its Glucose lowering effects are not additive