diabetes drugs · 2019-11-08 · alpha glucosidase inhibitors precose (acarbose), glyset (miglitol)...
TRANSCRIPT
DIABETES
DRUGSC RACHEL KILPATRICK, MD
WASHINGTON REGIONAL MEDICAL CENTER
FINANCIAL DISCLOSURES
SPEAKERS BUREAU FOR SANOFI AVENTIS, NOVO NORDISK, AMGEN,
ABBOTT
OBJECTIVES
IDENTIFY CLASSES OF DIABETES MEDICATIONS
IDENTIFY MEDICATIONS IN EACH CLASS AND THEIR ACTIONS
IDENIFY POTENTIAL SIDE EFFECTS
TYPES OF MEDICATIONS
Biguanides
Glucagon-like peptide-1 (GLP-1) agonists
Sodium-glucose Cotransporter-2 (SGLT2) inhibitors
Thiazolidinediones (TZDs)
Dipeptidyl peptidase IV (DDP-IV) Inhibitors
Sulfonylureas/Meglinides
Alpha-glucosidas inhibitors
Insulins
ADA 2019
Treatment
Guidelines.
METFORMIN
Metformin
Belongs to the biguanide class
Primary physiologic effects:
Reduces hepatic glucose
output of gluconeogenesis
Improves peripheral insulin
sensitivity
Initiation: Increase by 500mg
daily per week to max goal of
1000mg bid. (or once daily if XR)
Benefits: no hypoglycemia,
associated with weight loss, $4
Negative: renal limitation with GFR <45, potential for lactic
acidosis with IV contrast (hold 48
hours before and after), renal
failure, and heart failure; long
term potential for vitamin B12
deficiency
Renal disease: Ok to continue if
on it and GFR 30-45 mL/min but
cut dose by 50%, do not use if
GFR <30 mL/min
GLP-RECEPTOR AGONISTS
Diabetes. 2015.
64: 715-717.
GLP-1 Receptor Agonists Available brands:
Bydureon (XR exenatide)—once
weekly pen injector
Byetta (exenatide)—twice daily
(premeal) injections
Ozempic (semaglutide)—once
weekly injection
Trulicity (dulaglutide)—once
weekly pen injector
Victoza (liraglutide)—once daily
injection
Mechanism: improves insulin secretion from pancreas in a
glucose-dependent fashion,
reduces glucose output from
liver, slows gastric emptying,
neuro effects
Gradual initiation if possible to
help with side effects
Benefits: weight loss, no
hypoglycemia, possible CV
benefit (liraglutide)
Negative: side effects of
nausea, vomiting, risk of
pancreatitis, black box warning,
cost
SGLT-2 INHIBITORS
Sodium Glucose Cotransporter-2
Inhibitors (SGLT2)
Available drug options:
Invokana (canagliflozin)
Farxiga (dapagliflozin)
Jardiance (empagliflozin)
Stegatro (ertugliflozin)
Mechanism: inhibits SGLT-2
glucose reabsorption
Initiation: start low dose, then increase to high dose if needed
Benefits: weight loss, possible
CV benefit (canagliflozin, empagliflozin, dapagliflozin)
Negative: yeast infections, UTIs,
normoglycemic DKA, cost
THIAZOLIDINDEIONES
CMAJ. 2005.
Thiazolidinediones
Options
Actos (pioglitazone)
Avandia (rosiglitazone)
Mechanism: enhances glucose
and lipid metabolism through
action of PPAR-gamma
(peroxisome proliferator
activated receptor)
Improves insulin sensitivity and
decreases hepatic
gluconeogenesis
Benefits: cheap, once daily
dosing, no hypoglycemia
Negative: may precipitate
heart failure, associated with
fracture risk, theoretical concern
of bladder cancer
DPPIV-inhibitors
Dipeptidyl Peptide-IV inhibitors
(DPP-IV)
Available brands:
Januvia (sitagliptin)
Onglyza (saxagliptin)
Tradjenta (linagliptin)
Nesina (alogliptin)
Mechanism: inhibits the DPP-IV
enzyme that breaks down
endogenous GLP-1
Benefits: no hypoglycemia
Negative: limited effectiveness,
cannot be combined with GLP agonists, cost, nausea
SULFONYLUREAS / MEGLITINIDE
CMAJ. 2005.
Sulfonylureas / Meglitinides
Sulfonylureas:
Glipizide-short acting
Glyburide-short acting
Glimepiride-long acting
Meglitinides:
Starlix (nateglinide)
Prandin (repaglinide)
Mechanism: simulates insulin release from the pancreas
Benefits: effective, $4-CHEAP!
Negative: hypoglycemia,
weight gain, reduced
pancreatic reserve?
ALPHA GLUCOSIDASE INHIBITORS
Alpha glucosidase inhibitors
Precose (acarbose), Glyset
(miglitol)
Mechanism of Action: Inhibits
pancreatic alpha-amylase and
intestinal brush border alpha-
glucosidases, results in reduced
breakdown and absorption of
carbs. Reduces post-prandial
glucose and insulin spikes.
Start low dose and increase only
if tolerated.
Benefits: cheap, weight loss
Negative: flatulence (74%),
diarrhea (31%), abdominal pain
(19%), tends to improve with
time
INSULIN
Insulin Rapid-acting insulins: Apidra (glulisine),
Humalog (lispro), Novolog (aspart), Admelog (lispro), insulin lispro
Onset 15-30 minutes, Peak 1-2 hours,
Duration 3-5 hours, Best dose 10-15 minutes
before eating
More-rapid acting
Fiasp (novolog)-onset 15-18 minutes, peak
1.5-2.2, duration 5-7 hours
Long acting insulins
Lantus (glargine)-onset 3-4 hours, small
peak around 12 hours, 24 hour duration
Levemir (detemir)-onset 3-4 hours, small
peak around 6-8 hours, 12-23 hour duration
that is dose dependent
Tresiba (degludec)-onset 1 hour, peak 9
hours, 42 hour duration (25 hour half life)
Toujeo (glargine U-300)-onset 6 hours, peak
12-16 hours, duration 36 hours (19 hour half
life)
Basaglar (insulin glargine)-BIOSIMILAR,
onset 3-4 hours, peak 12 hours, duration 24
hours
Insulin Intermdiate acting: Novolin N, Humulin
N (NPH)
Onset of action 1-2 hours, peak action 6-
10 hours, duration 12+ hours that is dose
dependent
Short acting insulin: Novolin R, Humulin
R
Onset of action 15-30 minutes, 2-4 hours,
duration 6-8 hours
Mixed insulins:
Novolin 70/30, Humulin 70/30-mix of NPH
(70%)/Regular (30%)
Novolog 70/30-mix of NPH (70%), insulin
aspart (30%)
Humalog 75/25-mix of NPH (75%), insulin
lispro (25%)
Insulin/GLP-1 combinations
Soliqua—glargine/lixisenatide
100/33—100 units of glargine
and 33 mcg of lixisenatide per
pen.
Max dose 60 units
Start 15 units if on <15 units, start
30 units if on 30 units or greater.
Titrate like basal insulin
Xultophy—degludec/liraglutide
100/3.6—100 units of degludec
and 3.6 mcg of liraglutide per
pen.
Max dose of 50 units
Start 10 units and titrate like
basal insulin.
Pharmacokinetics
NEJM. 2005.
Insulin available without prescription
N
R
70/30
ADA 2019
Treatment
Guidelines.
ADA 2019
Treatment
Guidelines.
ADA 2019 Treatment
Guidelines.
ADA 2019 Treatment
Guidelines.
ADA 2019 Treatment
Guidelines.
Case 1
56 year old woman with a history of chronic kidney disease,
coronary artery disease, hypertension, hyperlipidemia presents with a1c of 9%
Medications: Metformin 1000mg bid, sitagliptin 100mg daily,
glipizide 5mg bid
Checks sugar 2-3 times per day
What would your first choice for therapy be in a patient like this?
Case 1
Kept on metformin 1000mg bid
Started on liraglutide and A1c improved to 7.5%.
Later started on basal insulin and titrated to dose of 28 units daily.
A1c improved to 6.9% without appreciable hypoglycemia.
Case 2
42 year old Hispanic man presented to clinic with an A1c of 12% on
metformin and 10 units of glargine insulin once daily.
Patient reported a history of weight loss. GAD antibodies were
negative, C-peptide was normal.
No other medical history.
What would your first choice for therapy be in a patient like this?
Case 2
Insulin.
Weight loss is red flag and A1c this elevated needs guaranteed
intervention.
Would start with under-dosed weight based dosing.
70 kg x 0.5 = 35 units/2 = 17 units
Increase to 15 units once daily
Start meal time insulin 5 units with meals.
Down the road if you wanted to consider non-insulin therapy, you could, but priority is to stop catabolic state.
SUMMARY
There are many drugs to choose from.
Its important to consider the side effects, risks, benefits of each
medication for each patient.
Optimize weight loss and insulin resistance.
Older less desirable drugs work in the right clinical setting
QUESTIONS?