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?