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Running head: TREATING TYPE II DIABETES MELLITUS

Pharmacological Guidelines for Treating Type II Diabetes Mellitus

Alyssa Matulich

University of Tennessee Chattanooga

Nursing 5800
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TREATING TYPE II DIABETES MELLITUS
Brief Overview of Disease Process

Type II diabetes mellitus is a multifactorial disease characterized by hyperglycemia,

insulin resistance, and impaired insulin secretion (Woo & Robinson, 2016). Insulin resistance

occurs due to the decrease responsiveness in beta cell stimulation by glucose in liver, muscle,

and adipose tissues (McCulloch & Robertson, 2016). The decrease in insulin secretion is

hypothesized to be caused by the insulin resistance that results in the compensatory increase in

insulin secretion that cannot be maintained by the pancreas (Hammer & Mcphee, 2014).

Because the pancreas becomes exhausted and insulin demands cannot be met and clinical

diabetes results (Hammer & Mcphee, 2014).

Appropriate Pharmacotherapeutic Selection

The goal of treatment for type 2 DM are near normal glucose levels, prevention of acute

complications such as hypoglycemia, prevention of the progression of the disease to target organ

damage, and appropriate patient self-oriented self-management (Woo & Robinson, 2016).

Pharmacological agents to treat type 2 DM are insulin and a various number or oral agents. The

initial drug of choice for treatment is Metformin a biguanide (McCulloch, 2017). Biguanides

work by decreasing hepatic glucose production by decreasing gluconeogenesis (Woo &

Robinson, 2016). Sulfonylureas are another class of oral agents that increase endogenous insulin

secretion by beta cells and improve the binding between insulin and insulin receptors (Woo &

Robinson, 2016). A common side effects with sulfonylureas are hypoglycemia and weight gain

(McCulloch, 2017). Sulfonylureas are first line in individuals with contraindications to

metformin (McCulloch & Robertson, 2016). Alpha-glucosidase inhibitors work in type 2 DM by

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competitively inhibiting and delaying the absorption of complex carbohydrates from the small

bowel (Woo & Robinson, 2016). These are not preferred because of poor efficacy and tolerance

and increased cost compared with other oral agents (McCulloch, 2017). Thiazolidinediones are

insulin sensitizers which results in the increased use of insulin by the liver, muscle cells, and

adipose tissues (Woo & Robinson, 2016). These oral agents are best used in combination

therapies and should be avoided in heart failure patients (McCulloch, 2017). Meglitinides work

on diabetes by acting as short acting insulin secreatgogues (Woo & Robinson, 2016). These

medications are not used commonly because of difficulty of adherence, GI side effects, and cost

(Woo & Robinson, 2016). Selective sodium glucose co-transporter 2 inhibitors work in the

kidneys by blocking glucose reabsorption and promoting glucose excretion (Woo & Robinson,

2016). These are best used in combination therapies and should be avoided in patients with

decreased GFR (McCulloch, 2017). Two additional agents that work in combination therapy for

diabetes by blocking DPP-4 activity are GLP-1 agonist and DPP-4 inhibitors (Woo & Robinson,

2016). DPP-4 inhibitors are oral agents and may be preferred in older patients or renal disease

patients where are GLP-1 agonist are injectable agents that may be more beneficial in younger

patients (Woo & Robinson, 2016). Monotherapy and treatment with two or three agents should

be considered before insulin therapy (McCulloch, 2017). Treatment with insulin vary for every

patient and the regimen should closely mimic endogenous insulin production (Woo & Robinson,

2016). Amylin hormone derivatives are other injectable options but are not popular due to nausea

and adherence (Woo & Robinson, 2016).

Pharmacokinetics and Pharmacodynamics

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Metformin, the only biguanide currently available, is the first line treatment for type 2

diabetes mellitus (McCulloch, 2018). Metformin, an oral medication, is absorbed via the

intestine and is not metabolized (Gong, Goswami, Giacomini, Altman, & Klein, 2012). Once

absorbed, metformin is distributed into the tissues including the intestine, liver and kidney by

organic cation transporters (Gong et al., 2012). It is excreted unchanged in the urine ("Up to

Date," 2018). Metformin’s mechanism of action is decreasing hepatic glucose output by

inhibiting gluconeogenesis, increasing insulin-mediated glucose utilization in peripheral tissues

after meals, and lowering serum free fatty acid concentration having an antilipolytic effect

(McCulloch, 2018). Metformin lowers basal and postprandial glucose (McCulloch, 2018). The

onset of action occurs within days with the maximum effect in two weeks ("Up to Date," 2018).

Metformin can be used in monotherapy or combination therapies. Metformin should not be used

with proton pump inhibitors because they inhibit the absorption (McCulloch, 2018). Monitor

blood glucose levels when using other medications that may cause hypoglycemia like SSRIs,

quinolones, salicylates, MAOIs, and androgens ("Up to Date," 2018).

Dosing for metformin is recommended to start at a low dose and increase slowly to

minimize GI symptoms and should be taken with meals ("Up to Date," 2018). Dosing increases

based on glycemic control. Pediatric use has been seen to be effective in patients 10-16 years old

("Up to Date," 2018). Usefulness in the other pediatric population has not been studied

(McCulloch, 2018). No dosing changes in cultural or ethnic differences. Metformin should not

be used in patients with severe renal dysfunction (McCulloch, 2018). It should be used with

caution in elderly patients because the risk of associated lactic acidosis increases with age
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(McCulloch, 2018). Metformin is pregnancy category B and found to cross the placenta

(McCulloch, 2018). Some studies have found that clearance may increase in pregnancy, so

dosing may need to be adjusted (McCulloch, 2018). Metformin may be used in breastfeeding

women, but it is detected in the mother breast milk so monitoring the infant for signs of

hypoglycemia is important (McCulloch, 2018). Metformin should be withheld on the day of

surgery and should be resumed when normal oral intake has been resumed (McCulloch, 2018).

Side Effects/ Adverse Effects

The most common side effects to Metformin are gastrointestinal (McCulloch, 2018).

Diarrhea, nausea, vomiting, and flatulence can be seen with Metformin use ("Up to Date," 2018).

Infection, flushing, palpitations, diaphoresis, weakness, decreased vitamin B12, skin rash, and

headache are also a side effects ("Up to Date," 2018). Metformin can cause hypoglycemia

(McCulloch, 2018). Patients should be educated on symptoms of hypoglycemia.

Contraindication/Cautions

Metformin use is contraindicated in patients with a hypersensitivity to the medication or

any of it components, severe renal dysfunction, and acute or chronic metabolic acidosis

(McCulloch, 2018). There is a boxed warning present for lactic acidosis and its associated side

effects like death, hypothermia, hypotension, and resistant bradyarrhythmia ("Up to Date,"

2018). Vitamin B12 deficiency may be associated with long term use (McCulloch, 2018).

Safety and Monitoring

Patients should be monitored for hypoglycemia daily and hemoglobin A1c should be

monitored twice annually in patients who have stable glycemic control (McCulloch, 2018).
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Vitamin B12 should be monitored with long term use (McCulloch, 2018). Patient renal function

should be monitored prior to starting metformin and at least once annually thereafter ("Up to

Date," 2018). There are no abuse potentials for metformin. Metformin should not be

discontinued without talking to the patient’s doctor (McCulloch, 2018). Depending on the dosage

metformin dosage may be decreased over time or stopped completely without concern

(McCulloch, 2018).

Extraneous Prescribing Issues

There are no ethical or legal considerations when prescribing Metformin for type 2 DM.

The prescription will be written based on the patient’s hemoglobin A1C and needed glycemic

control. Patient education should include the side effects of Metformin, to take with food to

decrease GI upset and at the same time every day (McCulloch, 2018). Patients should be familiar

with the signs and symptoms of hypoglycemia (McCulloch, 2018). Alcohol use should be

discouraged in patients taking metformin (McCulloch, 2018). In order to maximize the

effectiveness of therapy, diabetes self-management education should be done with the patient

(McCulloch, 2018).
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References

Gong, L., Goswami, S., Giacomini, K. M., Altman, R. B., & Klein, T. E. (2012). Metformin

pathways: Pharmacokinetics and pharmacodynamics. Pharmacogenetics and genomics,

22, 820-827. http://dx.doi.org/10.1097/FPC.0b013e3283559b22.

Hammer, G. D., & Mcphee, S. J. (2014). Pathophysiology of disease: An introduction to clinical

medicine (7th ed.). : McGraw-Hill Education .

McCulloch, D. K. (2017, April 13). Management of persistent hyperglycemia in type 2 diabetes

mellitus. Up to Date. Retrieved from https://www-uptodate-

com.proxy.lib.utc.edu/contents/management-of-persistent-hyperglycemia-in-type-2-

diabetes-mellitus?search=diabetes

%20medications&source=search_result&selectedTitle=4~150&usage_type=default&disp

lay_rank=4

McCulloch, D. K. (2018, February 15). Metformin in the treatment of adults with type 2 diabetes

mellitus. Up to Date. Retrieved from https://www-uptodate-

com.proxy.lib.utc.edu/contents/metformin-in-the-treatment-of-adults-with-type-2-

diabetes-mellitus?search=type%202%20diabetes%20mellitus

%20%20treatment&source=search_result&selectedTitle=5~150&usage_type=default&di

splay_rank=5

McCulloch, D. K., & Robertson, R. P. (2016, November 17). Pathogenesis of type 2 diabetes

mellitus. Up to Date. Retrieved from https://www-uptodate-

com.proxy.lib.utc.edu/contents/pathogenesis-of-type-2-diabetes-mellitus?

search=pathophysiology%20diabetes%20type
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%202&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=

Metformin: Drug information. (2018). Retrieved from https://www-uptodate-

com.proxy.lib.utc.edu/contents/metformin-drug-information?search=Metformin

%20pharmacokinetics&source=search_result&selectedTitle=1~148&usage_type=default

&display_rank=1

Woo, T. M., & Robinson, M. V. (2016). Pharmacotherapeutics for advanced practice nurse

prescribers (4th ed.). Philadelphia, PA: F.A. Davis Company.