1. 1010
(Table). The now vast arsenal of
available medications for treating
diabetes has made finding a
universal treatment plan virtually
impossible. Additionally, new drug
classes mean new potential adverse
effects that have not been
investigated thoroughly because of
the limited number of long-term
studies. Potential adverse effects
must be carefully considered before
beginning treatment because type 2
diabetes is often accompanied by
one or more comorbidities.
Experts contend that there is not
now nor ever will be an ideal
treatment plan for type 2 diabetes.
The ADA suggests that a patient-
centered approach will likely yield
the most favorable outcomes.
Involving patients in developing their
treatment plans and carefully
considering each person’s medical
and lifestyle constraints can increase
compliance and subsequently the
overall effectiveness of diabetes
treatment.
Given the abundance of available
noninsulin diabetes medication and
the recent shift from an algorithmic
to a patient-centered approach,
registered dietitian nutritionists
(RDNs) will begin seeing modifications
in both the types and combinations
of drugs being used to treat type 2
diabetes. It is important to note that
no single diabetes drug class is
superior to another. Each new drug
class moves clinicians closer to the
goal of providing customized
treatment of type 2 diabetes.
Becoming as well-versed in
pharmacologic treatment as they
are in the nutritional approach to
diabetes not only will increase the
credibility of RDNs, but it can
strengthen their role within the
health care team. Using the nutrition
care process can equip RDNs with
important tools for implementation
of the patient-centered approach.
They can obtain important
information to assist the health care
team in developing individualized
type 2 diabetes treatment plans.
References:
1. Centers for Disease Control and
Prevention. Distribution of
first-listed diagnoses among
hospital discharges with diabetes
as any listed diagnosis, adults aged
18 years and older, United States,
2010. Diabetes Public Health
Resource. 2014. http://www.cdc.
gov/diabetes/statistics/hosp/
adulttable1.htm. Accessed
December2014.
2. Inzucchi SE, Bergenstal RM, Buse
JB, et al; American Diabetes
Association (ADA); European
Association for the Study of
Diabetes (EASD). 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). Diabetes Care.
2012;35:1364–1379.
According to the latest data from the
National Hospital Discharge Survey,
diabetes is the second most common
diagnosis among hospital discharges
in America (1). This fact not only
highlights the grim epidemiologic
characteristics of diabetes, but it is a
clear indication that the disease is
not being effectively managed.
Historically, in an effort to create a
standardized treatment approach,
type 2 diabetes was treated using
a pharmacologic algorithm. With
the exception of diet and lifestyle
modification being the first step in
defense against the disease and
metformin being the second line of
defense, the algorithmic approach
proved ineffective due to the
individualized nature of diabetes.
A position statement published by
the American Diabetes Association
(ADA) and the European Association
for the Study of Diabetes (EASD) in
2012 suggested that“Glycemic
management in type 2 diabetes
mellitus has become increasingly
complex and, to some extent,
controversial, with a widening array
of pharmacological agents now
available, mounting concerns about
their potential adverse effects and
new uncertainties regarding the
benefits of intensive glycemic control
on macrovascular complications”(2).
Since the introduction of
sulfonylureas 60 years ago, many
pharmaceutical companies have
focused on the development of
noninsulin diabetes medications
An Update on Noninsulin Treatment for Type 2 Diabetes
Joline Parer, dietetic student
Harvey, IL

2. 11
Sulfonylureas (United Stated Food and Drug
Administration Approval – 1955): glimepiride,
glyburide, glipizide
• Mechanism of Action: stimulates beta cells in the
pancreas to produce more insulin (long-acting)
• Dosing: once or twice daily with meals
• Adverse effects: hypoglycemia, weight gain
• May not be suitable for: people at high risk for
hypoglycemia
Meglinitides (1997): repaglinide, nateglinide
• Mechanism of Action: stimulates beta cells in the
pancreas to produce more insulin (short-acting)
• Dosing: with every meal
• Adverse effects: hypoglycemia, weight gain
• May not be suitable for: people at high risk for
hypoglycemia
Bigaunides (1994): metformin
• Mechanism of Action: decreases glucose production
in the liver
• Dosing: once or twice daily with meals OR at bedtime
• Adverse effects: gastrointestinal distress (may be
less when taken with meals)
• May not be suitable for: people with liver disease
Thiazolidinediones (1997): rosiglitazone, pioglitazone
• Mechanism of Action: increases insulin sensitivity in
muscle and fat cells (effects on blood glucose may
take 4-6 weeks or more)
• Dosing: once daily
• Adverse effects: fluid retention
• May not be suitable for: people with heart disease
Alpha-glucosidase Inhibitors (1995): acarbose, miglitol
• Mechanism of Action: slows digestion of
carbohydrates by inhibiting alpha-glucosidases in
the small intestine, lowers blood glucose
concentrations following carbohydrate consumption
• Dosing: with first bite of every meal
• Adverse effects: gastrointestinal distress
• May not be suitable for: people with gastrointestinal
dysfunction
Glucagon-like peptide-1 (GLP-1) Receptor Agonists
(2005): exenatide, exenatide XR, liraglutide, albiglutide,
dulaglutide
GLP-1 is an incretin hormone that is released during
meals from endocrine cells in the gut. It is responsible
for stimulating glucose-induced insulin secretion,
suppressing glucagon secretion, inhibiting gastric
emptying, and reducing appetite and food intake.
Levels of GLP-1 are enzymatically inactivated and
reduced to fasting levels by the dipeptidyl
peptidase-4 (DPP-4) enzyme. Only 10% to 20% of the
GLP-1 hormone that enters the bloodstream is
biologically active due to the activity of DPP-4 (4).
• Mechanism of Action: mimics the actions of GLP-1
for an extended period of time (due to resistance to
DPP-4)
• Dosing: injected twice daily (exenatide), once daily
(liraglutide), or once weekly (exenatide XR,
albiglutide, dulaglutide)
• Adverse effects: mild gastrointestinal distress
• May not be suitable for: people with gastrointestinal
dysfunction
DPP-4 inhibitors (2006): sitagliptin, saxagliptin,
linagliptin, alogliptin
• Mechanism of Action: inhibits the DPP-4 enzyme,
allowing the GLP-1 hormone to remain active for an
extended period of time
• Dosing: once daily
• Adverse effects: no notable adverse effects
• May not be suitable for: people with renal
dysfunction
Sodium-glucose cotransporter 2 (SGLT-2) Inhibitors
(2013): canagliflozin, dapagliflozin, empagliflozin
• Mechanism of Action: inhibits SGLT-2 (which is
responsible for 90% of glucose reabsorption by the
kidneys), causing excess glucose to be excreted
through urine
• Dosing: once daily
• Adverse effects: vaginal yeast infections, urinary
tract infections, diuresis
• May not be suitable for: people with renal
dysfunction
Table. Classes of Noninsulin Diabetes Medications (3)
3. Diseases and Conditions. Type 2
Diabetes. Compare Diabetes
Medication. Rochester, MN: Mayo
Clinic; 2014. http://www.mayo
clinic.org/diseases-conditions/
type-2-diabetes/in-depth/
diabetes-treatment/art-
20051004?pg=2. Accessed
December 2014.
4. Drucker DJ, Nauck MA. The incretin
system: glucagon-like peptide-1
receptor agonists and dipeptidyl
peptidase-4 inhibitors in type 2
diabetes. Lancet. 2006;368:
1696–1705.