Comparative Analysis: Exenatide vs. Other Diabetes Treatments

This report investigates the efficacy of exenatide, a GLP-1 receptor agonist, in the treatment of type 2 diabetes mellitus (T2DM). The study, involving randomized and controlled populations in three phases (Duration-2, -3, and -4), compared exenatide's performance against conventional therapies like metformin, sitagliptin, pioglitazone, and insulin glargine. The research evaluated exenatide's impact on glycemic control, cardiovascular risk factors (blood pressure, body weight, HbA1c, and lipids), and the number needed to treat (NNT) to achieve recommended treatment goals. Findings indicated that exenatide, when used twice daily, improved glycemic control, reduced body weight, and lowered cardiovascular risks. The study highlighted exenatide's superiority in reducing HbA1c compared to sitagliptin and pioglitazone, with a significant absolute benefit increase (ABI) in meeting T2DM management goals, particularly regarding glycemic control and cardiovascular risk reduction. Although associated with adverse effects like nausea and diarrhea, exenatide demonstrated a favorable safety profile and effectiveness in the treatment of T2DM.

Running head: TREATMENT OF DIABETES 1
Treatment of Diabetes
Student’s Name
Institutional Affiliation
Treatment of Diabetes

TREATMENT OF DIABETES 2
Introduction
Type 2 diabetes mellitus (T2DM) is a disease caused by the increase in blood sugars,
hyperglycemia. Diabetes results in cardiovascular diseases (CVA) and myocardial infarction.
Long-term management of diabetes mellitus is therefore not just a reduction in hyperglycemia
(Stratton et al., 2000), but glycemic control would too significantly benefit the T2DM patients.
With glycemic control, cardiovascular risk factors for example blood pressure, body weight,
glycated hemoglobin (HbA1c) and lipids are all in check. This is known as the multifactorial
approach for the t2dm treatment as it’s holistic in addressing the disease. Conventional methods
or commonly prescribed therapies for treating diabetes uses insulin glargine, sitagliptin, and
pioglitazone. This paper explores the effectiveness of exenatide in glycemic control towards
achieving recommended goals for T2DM treatment (Diabetes, 1998).
Exenatide is a GLP-1 receptor agonist that does reduce not only hyperglycemia but also
improves the body weight, blood pressure and lipid profiles in patients with T2DM. When used
twice a day, exenatide has proven to reduce the risk of cardiovascular events and hospitalizations
compared with other glucose-lowering therapies. An important measure in this study is the
number needed to treat (NNT) or the absolute benefit increase (ABI) which is the percentage of
patients who reach the recommended treatment goals from each of the therapeutic groups.
Methodology
The study involved 3 randomized and controlled population organized in 3 phases;
Duration -2, -3 and 4. Patients from each of the 3 phases/studies received a background therapy.
Duration-2 were treated with metformin, duration-3 received metformin with or without
sulfonylurea whereas duration 4 were suboptimally controlled through diet and exercise. All
patients had T2DM, their baseline glycated hemoglobin levels were in the range of 7.1 to 11.0%

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and a body mass index of 25-45 kg/m2. Also, all of the patients were over 18 years of age, and
their medical history portrayed a stable body weight before the screening visit (Bonds et al.,
2010).
In all the trials, a standard dose of medication was administered for 26 weeks. Duration -
2 patient received 2 mg of exenatide twice weekly and 100 mg of sitagliptin each day. 45 mg of
pioglitazone per day could be used in place of sitagliptin. Duration-3 patients received either 2
mg of exenatide twice weekly or 4.0 to 5.5 mmol/L of insulin glargine each day. Duration-4
patients were considered as ‘drug naïve’ and received 2 mg of exenatide twice weekly, 2000 mg
of metformin a day and either a 100 mg of sitagliptin or 45 mg of pioglitazone a day. Both
metformin and pioglitazone underwent weekly increments to achieve target doses for glycemic
control (Meloni et al., 2013).
Study Findings
It is worth noting that metformin is the commonly recommended therapy for treatment of
T2DM. Results from the study show that exenatide and metformin provided similar
improvement toward glycemic control. However, with exenatide, patients are in a better position
as it reduces both the body weight and risks of hypoglycemia. Also, at 95% confidence interval,
the study favored exenatide over metformin for its ability to reduce glycated hemoglobin and
fasting blood glucose to ≤6.5% and <6.99 mmol/L.
Comparing exenatide and sitagliptin in duration-2 and duration-4, the trials show that
exenatide is more superior in reducing HbA1c (-1.5%) as compared to 0.9% (sitagliptin). The
greatest goal in the trial was that exenatide was able to achieve <7%, recommended goal for the
HbA1c. In both the studies, ABI favored exenatide compared to sitagliptin.

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Duration 2 and duration 4 studies aimed at comparing the effectiveness of exenatide
against pioglitazone in treatment of type 2 diabetes. Exenatide was superior to duration-2 patient
where a reduction in HbA1c was at -1.5% against -1.2% for pioglitazone. Also, ABI favored
exenatide over pioglitazone. However, there was no significance in reduction of the HbA1c
using exenatide (-1.5%) and using pioglitazone (-1.6%) in duration-4 patients.
Duration-3 studies aimed at comparing exenatide and insulin glargine. Exenatide resulted
in -1.5% reduction in HbA1c while insulin glargine achieved a -1.3%. Out of all the four
composite goals, exenatide was significantly favored for meeting the recommended targets.
From all the studies, exenatide was associated with the most frequent number of adverse effects
on patients with the highest of these events being 7%. The adverse events included nausea,
diarrhea, headache, nasopharyngitis, and reactions at the point of injection (Meloni et al. 2013).
Discussion
As was mentioned above, treatment and management of type 2 diabetes revolve about
four compost goals. According to studies (Ismail-Beigi et al., 2010), not all therapies are in a
position to achieve the recommended goals. For this reason, any therapy capable of achieving the
most of the goals is the most appropriate. Considering glycemic goal, exenatide done twice
weekly assisted a larger portion of patients to achieve HbA1c ≤6.5% after the 26 weeks of the
trial.
Glycemic control goes hand in hand with control of cardiovascular risk factors,
hyperglycemia. Unlike most therapies, GLP-1 receptor agonists like exenatide are associated
with weight loss and reduced risks of hypoglycemia. From the study, exenatide provided a
significant ABI in achieving this goal; no weight gain and no hypoglycemia. In the three studies,
exenatide was at the rescue of 47 patient, representing 48% of the total population in achieving

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control over cardiovascular risk factors. This was against the 10% assistance from pioglitazone.
As was mentioned above, metformin was no inferior from exenatide, but from the ABI
perspective, exenatide was significantly favored for its effectiveness in achieving the
recommended T2DM management goals (Meloni et al. 2013). In conclusion, the safety and
efficacy of exenatide when used twice a week will not only help patients reduce cardiovascular
risks but will help reduce the morbidity and mortality of patients suffering from diabetes.

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