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Management of Type 2 Diabetes Mellitus with Oral Medications

Diabetes | January 5, 2016 | Author: The Super Pharmacist


Management of Type 2 Diabetes Mellitus with Oral Medications

What Is Type 2 Diabetes?

Type 2 diabetes is the most common form of diabetes. In type 2 diabetes, the body produces insulin, but the body does not use it properly. Insulin is a hormone that regulates the movement of sugar (glucose) into cells. Sometimes, the body produces more insulin than is really needed, but the blood glucose remains high. This is because the body's cells are resistant to the effects of insulin. In other cases of type 2 diabetes, the body does not produce enough insulin to maintain a normal blood sugar level. Physicians and scientists believe that type 2 diabetes is caused by many factors, including insufficient insulin and insulin resistance. They increasingly believe that the relative contribution each factor makes toward causing diabetes varies from person to person.1

What Is the Treatment Protocol for Type 2 Diabetes?

Medical professionals who are involved in diabetes care will admit that considerable controversy revolves around the issue of the best approach to manage individuals with diabetes.2 Given the fact that most diabetic patients are not seen in specialised centers, the argument is made that the broadest approach that can be applied to the greatest number of patients should be followed. On the opposite side of the argument, there are those who advocate following a specific, defined pharmaceutical approach to every patient. The latter approach would reserve the more costly newer therapies for cases where traditional medications have failed. In actual practice, however, most medical professionals follow an intermediate strategy where a particular therapy is chosen after carefully considering all relevant factors in a given patient (eg, any co-occurring illnesses, how long the patient has had diabetes, and the patient's resources). The approach to consider all factors and individualise therapy is the approach taken by the American Diabetes Association–European Association for the Study of Diabetes (ADA-EASD) and is outlined in their 2012 position statement.3 The need to follow “individualised” therapy was clearly supported by the findings of the Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE), and Veterans Affairs Diabetes Trial (VADT) studies when evaluating cardiovascular end points.4-6 The accumulated results from these type 2 diabetes cardiovascular trials suggest that not everyone benefits from aggressive glucose management. It follows that it is important to individualise treatment targets.4-7 Management of Type 2 Diabetes Mellitus with Oral MedicationsThis approach is called patient-centered care. Patient-centered care is defined as an approach to “providing care that is respectful of and responsive to individual patient preferences, needs, and values and ensuring that patient values guide all clinical decisions."8 This should be the organising principle for individuals with any chronic disease, but given the uncertainties in terms of choice or sequence of therapy, it is particularly appropriate in type 2 diabetes. The hemoglobin A1c, or glycosylated hemoglobin, is a blood test that serves as a marker for the average blood glucose levels in any given patient over the past 3 months. It is a measure of how well controlled the blood glucose level has been over that length of time.

How Is the HbA1c Target Chosen for Individual Patients?

The ADA's “Standards of Medical Care in Diabetes” recommends lowering HbA1c  to <7.0% in most patients to reduce the incidence of microvascular disease.9 This can be achieved with a mean plasma glucose of ∼8.3–8.9 mmol/L (∼150–160 mg/dL); ideally, fasting and pre-meal glucose should be maintained at <7.2 mmol/L (<130 mg/dL) and the postprandial glucose at <10 mmol/L (<180 mg/dL). It is well established that the risk of microvascular and macrovascular complications is related to hyperglycemia (high blood sugar levels), as measured by HbA1c.10 However, not everyone benefits from aggressive glucose management. It follows that it is important to individualise treatment targets.4-7 More stringent HbA1c  targets (eg, 6.0–6.5%) might be considered in select patients (with short disease duration, long life expectancy, no significant CVD) if this can be achieved without significant hypoglycemia or other adverse effects of treatment.11,12 Conversely, less stringent HbA1c goals — e.g., 7.5–8.0% or even slightly higher—are appropriate for patients with a history of severe hypoglycemia (low blood sugar), limited life expectancy, advanced complications, extensive co-occurring conditions and those in whom the target is difficult to attain despite intensive self-management education, repeated counselling, and effective doses of multiple glucose-lowering agents, including insulin.11,13 The elements that are recommended to guide the physician in choosing a HbA1c target for a specific patient are shown in Table 1.2 Table 1. Depiction of the elements of decision making in regard to the appropriate target for the HbA1C level. Whenever possible, such decisions should be made in conjunction with the patient, reflecting his or her preferences, needs, and values.2 [table id=38 /]

What Is the First Line of Treatment for Type 2 Diabetes?

The first line of treatment for type 2 diabetes is weight reduction. This can be achieved either with diet alone or in conjunction with medical or surgical intervention. Weight reduction improves glycaemic control and other cardiovascular risk factors. Dietary advice should be personalised.14  Foods high in fibre (such as vegetables, fruits, whole grains, and legumes), low-fat dairy products, and fresh fish should be emphasised.15-17 Along with weight loss, as much physical activity as possible should be promoted, ideally aiming for at least 150 min/week of moderate activity including aerobic, resistance, and flexibility training.18 If diet and exercise are inadequate, the next line of treatment is oral medication.

What Are the Different Oral Medications that Are Used to Treat Type 2 Diabetes?

Management of Type 2 Diabetes Mellitus with Oral MedicationsOral medications for the treatment of type 2 diabetes include:

  1. Biguanides,
  2. Sulphonylureas,
  3. Meglitinides,
  4. Thiazolidinediones,
  5. DPP-4 inhibitors,
  6. Alpha-glucosidase inhibitors,
  7. Bile acid sequestrants,
  8. SGLT2 inhibitors, and
  9. Combination pills.19


Biguanides lower blood glucose levels primarily by decreasing the amount of glucose produced by the liver. Metformin, a biguanide, remains the most widely used first-line type 2 diabetes drug. Metformin also helps to lower blood glucose levels by making muscle tissue more sensitive to insulin so glucose can be absorbed.19


Sulphonylureas stimulate the beta-cells of the pancreas to release more insulin. Sulfonylurea drugs have been in use since the 1950s. Chlorpropamide is the only first-generation sulfonylurea still in use today. The second generation sulphonylureas are used in smaller doses than the first-generation drugs. There are three second-generation drugs: glipizide,  glyburide and glimepiride. These drugs are generally taken one to two times a day, before meals. All sulfonylurea drugs have similar effects on blood glucose levels, but they differ in side effects, how often they are taken, and interactions with other drugs.19 Because these medicines can cause low blood glucose (hypoglycaemia), it is recommended to carry a source of carbohydrate with you.


Meglitinides are drugs that also stimulate the beta-cells to release insulin. Repaglinide and nateglinide are meglitinides. They are taken before each of three meals. Because sulphonylureas and meglitinides stimulate the release of insulin, it is possible to have hypoglycemia (low blood glucose levels).19 However, meglitinides are less likely to cause hypoglycaemia than sulphonylureas.


Rosiglitazone and pioglitazone are in a group of drugs called thiazolidinediones. These drugs help insulin work better in the muscle and fat and also reduce glucose production in the liver. The first drug in this group, troglitazone, was removed from the market because it caused serious liver problems in a small number of people. So far, rosiglitazone and pioglitazone have not shown the same problems, but users are still monitored closely for liver problems as a precaution. Both drugs appear to increase the risk for heart failure in some individuals, and there is debate about whether rosiglitazone may contribute to an increased risk for heart attacks. Both drugs are effective at reducing HbA1C and generally have few side effects.19

DPP-4 Inhibitors

A new class of medications called DPP-4 inhibitors help improve HbA1C levels without causing low blood sugar.They work by preventing the breakdown of a naturally occurring compound in the body, GLP-1. GLP-1 reduces blood glucose levels in the body, but is broken down very quickly so it does not work well when injected as a drug itself. By interfering in the process that breaks down GLP-1, DPP-4 inhibitors allow it to remain active in the body longer, lowering blood glucose levels only when they are elevated. DPP-4 inhibitors do not tend to cause weight gain and tend to have a neutral or positive effect on cholesterol levels. Sitagliptin, saxagliptin, linagliptin, alogliptin are the DPP-4 inhibitors currently on the market.19

Alpha-glucosidase inhibitors

Acarbose and miglitol are alpha-glucosidase inhibitors. These drugs help the body to lower blood glucose levels by blocking the breakdown of starches, such as bread, potatoes, and pasta in the intestine. They also slow the breakdown of some sugars, such as table sugar. Their action slows the rise in blood glucose levels after a meal. They should be taken with the first bite of a meal. These drugs may have side effects, including gas and diarrhoea.19

SGLT2 Inhibitors

Glucose in the bloodstream passes through the kidneys, where it can either be excreted or reabsorbed.  Sodium-glucose transporter 2 (SGLT2) works in the kidney to reabsorb glucose, and a new class of medication, SGLT2 inhibitors, block this action, causing excess glucose to be eliminated in the urine. Canagliflozin and dapagliflozin are SGLT2 inhibitors that have recently been approved by the FDA to treat type 2 diabetes.  Because they increase glucose levels in the urine, side effects can include urinary tract and yeast infections.19

Bile acid sequestrants

The bile acid sequestrant, colesevelam, is a cholesterol-lowering medication that also reduces blood glucose levels in patients with diabetes. Bile acid sequestrants help remove cholesterol from the body, particularly low-density lipoprotein (LDL) cholesterol, which is often elevated in people with diabetes.  These medications reduce LDL cholesterol by binding with bile acids in the digestive system; the body in turn uses cholesterol to replace the bile acids, which lowers cholesterol levels. The mechanism by which colesevelam lowers glucose levels is not well understood. Because bile acid sequestrants are not absorbed into the bloodstream, they are usually safe for use by patients who may not be able to use other medications because of liver problems. Because of the way they work, they can cause flatulence and constipation.19

Combination pills

Because the drugs listed above act in different mechanisms to lower blood glucose levels, they may be used together. For example, a biguanide and a sulfonylurea may be used together. Many combinations can be used. Though taking more than one drug can be more costly and can increase the risk of side effects, combining oral medications can improve blood glucose control when taking only a single pill does not have the desired effects. Switching from one single pill to another is not as effective as adding another type of diabetes medicine.19 Australia's best online pharmacy


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  3. Inzucchi SE, Bergenstal RM, Buse JB, et al. 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 Care2012;35:1364–1379.
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  8. Committee on Quality of Health Care in America: Institute of Medicine. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, DC, The National Academies Press, 2001.
  9. American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care2011;34(Suppl. 1):S11–S61.
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  11. Ismail-Beigi F,  Moghissi E,  Tiktin M, et al. Individualizing glycemic targets in type 2 diabetes mellitus: implications of recent clinical trials. Ann Intern Med2011;154:554–559.
  12. Akalin S,  Berntorp K,  Ceriello A, et al. Global Task Force on Glycaemic Control.Intensive glucose therapy and clinical implications of recent data: a consensus statement from the Global Task Force on Glycaemic Control. Int J Clin Pract2009;63:1421–1425.
  13. Lee SJ, Eng C. Goals of glycemic control in frail older patients with diabetes. JAMA 2011;305:1350–1351.
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  19. What are my options? American Diabetes Association. Updated 3 March 2015. Accessed 19 April 2015.
  20. Oral diabetes medications summary chart. (n.d.) Accessed 19 April 2015.
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