Type 2 Diabetes: A Guide to Prevention and Treatment

Research on the prevention and treatment of Type 2 diabetes has evolved dramatically over the past decade. There is now more information than ever before on the beneficial effects of diet and exercise, both to prevent the onset of diabetes and as a critical part of its treatment. Unfortunately, several new classes of diabetes medications with well-documented dangers have been approved by the Food and Drug Administration (FDA) in the last decade. Worst Pills, Best Pills News has kept readers up to date as important new information emerges. Here, we summarize the best information on Type 2 diabetes prevention and treatment.

What is diabetes?

Diabetes (diabetes mellitus) is a malfunction of the body’s system that regulates glucose (sugar) through the production and use of insulin. When the body does not produce enough insulin, or when cells fail to respond normally to insulin, sugar is not removed from the bloodstream and high levels accumulate.[1]

This abnormality in glucose metabolism can lead to kidney disease, blindness, nerve damage, foot ulcers, hardening of the arteries, heart disease and increased risk for infections. Three out of four diabetics die of cardiovascular (heart and/or blood vessel) disease related to their diabetes. The majority of these deaths are from heart disease, predominantly heart attacks.[2]

Less than 10 percent of Americans with diabetes have Type 1 diabetes, a condition in which the pancreas is unable to produce insulin and which usually starts at a young age.[3] People with Type 1 diabetes require daily insulin injections and must adhere to a strict diet to control the level of sugar in their blood.[4]

Most diabetics have Type 2 diabetes. People with this condition typically make less insulin and, more importantly, do not respond normally to insulin, meaning they require greater amounts than a nondiabetic person (this is called “insulin resistance”).[5] This combination of limited insulin production and increased insulin requirements leads to the loss of control of blood glucose.

Diet and exercise for treating and preventing Type 2 diabetes

About 90 percent of children and more than half of adults with Type 2 diabetes are overweight or obese.[6],[7] Obesity itself causes insulin resistance, and weight loss is the cornerstone of diabetes prevention and treatment for overweight patients.

Diet and exercise programs are highly effective in preventing Type 2 diabetes among people who are at high risk for the disease. The landmark study establishing this, published in the New England Journal of Medicine in 2002, demonstrated that lifestyle intervention (an intensive weight loss diet and exercise program for 24 weeks, with monthly sessions for two to 4.5 years afterwards) not only resulted in weight loss but also reduced the risk of developing diabetes by more than 50 percent, making it even more effective at preventing diabetes than the diabetes drug metformin (GLUCOPHAGE).[8]

Similar results have been demonstrated in other studies. In 2013, researchers published a study that analyzed combined data from nine randomized, controlled trials among people at high risk for diabetes who were randomly assigned to receive either an intensive diet and exercise program ranging in length from six to 72 months or usual care (which varied depending on the study but could include advice from a family physician, standard materials or advice on diet or exercise, food diaries, annual education sessions, or no additional help at all).[9] Across all nine studies, people who used intensive diet and exercise were one-third as likely to develop diabetes as those in the usual care control groups at the end of the intensive program. Even 10 years after the lifestyle program ended, those treated in the program were still 20 percent less likely to have been diagnosed with diabetes.[10]

Lifestyle changes should be tried before considering drug therapy. Start by asking your doctor for help planning a simple diet designed to control your diabetes. The basic plan should be to limit carbohydrates, especially those coming from sugar, and include sources of protein and healthy fat to balance out meals.[11] If trying to lose weight, you should also limit overall calories.[12]

A regular exercise program is also recommended. Exercise helps to lower blood sugar and reduce weight. The physical activity does not have to be strenuous; walking is often the best form of exercise. Make sure you check with your doctor to see if you have any health conditions or complications that might limit your exercise program.[13]

Changing your lifestyle is not always easy. Signing up for regular nutritional counseling, sessions with an exercise adviser or a diabetes support group may help. The American Diabetes Association (ADA) can assist you in finding programs in your area. You can find your local office by visiting www.diabetes.org or by calling 800-DIABETES (800-342-2383).[14]

Oral medications for Type 2 diabetes

Patients should try to achieve blood sugar control using diet and exercise for up to nine months before considering drug treatment. Oral medications are the next step if blood sugar remains uncontrolled. Pills are effective at reducing blood sugar levels, but they do not treat the underlying cause of the disease and some actually undermine the purpose of treating diabetes by increasing the chance of dying from cardiovascular disease.

Experts recommend metformin for patients who have tried and failed to control their blood sugar through diet and exercise. One of the most effective drugs at lowering blood sugar, metformin does not cause weight gain, has few side effects and is available at low cost.[15],[16] In the UK Prospective Diabetes Study (UKPDS), published in The Lancet in 1998, over 700 subjects with newly diagnosed Type 2 diabetes were randomly assigned to receive intensive metformin therapy aimed at achieving near-normal blood sugar levels or to receive conventional care selected by their physicians.[17] Subjects in both groups received dietary counseling[18] and could also receive glyburide (DIABETA, GLYNASE, MICRONASE), a type of drug known as a sulfonylurea, or insulin if their blood sugars were too high.[19] After a median time of 10.7 years, subjects in the metformin group had lower blood sugar than those in the control group.[20] They also had a statistically significant 36 percent lower overall mortality.[21]

If diet and exercise combined with metformin fail to control blood sugar, patients should discuss with their doctors whether to add a second- or third-generation sulfonylurea or move directly to insulin therapy. Sulfonylureas are as effective as metformin at reducing blood sugar.[22] However, these drugs also cause weight gain, fluid retention and hypoglycemia (low blood sugar), and they have not been proven to be effective at reducing mortality when used without metformin.[23]

Do not use the first-generation sulfonylureas — tolbutamide (ORINASE), acetohexamide (DYMELOR), tolazamide (TOLINASE) and chlorpropamide (DIABINESE) — as these drugs may actually increase cardiovascular risks and mortality relative to a placebo.[24],[25] Second- or third-generation sulfonylureas, such as glyburide and glipizide (GLUCOTROL) or glimepiride (AMARYL), have not demonstrated the same risks and are less likely to cause dangerously low blood sugar.[26]

None of the newer classes of diabetes drugs offer any meaningful clinical improvements over metformin or the sulfonylureas, and most carry serious, unique risks.

We recommend that you do not use alpha-glucosidase inhibitors, including acarbose (PRECOSE), as these are less effective at lowering blood sugar relative to metformin and sulfonylureas, and cause unpleasant gas and other digestive symptoms.[27]

Do not use amylin agonists, including pramlintide (SYMLIN), which is also less effective at lowering blood sugar and causes unpleasant digestive symptoms. Pramlintide is approved only as an injection used in addition to insulin, meaning many patients who take this drug may be able to achieve similar results by simply adjusting their insulin dosage.[28]

Do not use the glinides — repaglinide (PRANDIN) and nateglinide (STARLIX) — because they have a similar risk for weight gain as sulfonylureas and less is known about their safety risks relative to older classes of drugs.[29] Nateglinide is also less effective at lowering blood sugar.

Do not use rosiglitazone (AVANDIA) and pioglitazone (ACTOS). These drugs carry many dangerous side effects, including congestive heart failure.[30],[31] Rosiglitazone has been shown to significantly increase risk of heart attack and death from cardiovascular causes, and pioglitazone is associated with an increased risk of bladder cancer.[32],[33]

Do not use any of the GLP-1 agonists and DPP-4 inhibitors, categories of drugs that include exenatide (BYETTA, BYDUREON), liraglutide (VICTOZA), sitagliptin (JANUVIA, JANUMET, JANUMET XR, JUVISYNC), saxagliptin (ONGLYZA, KOMBIGLYZE XR), linagliptin (TRADJENTA, JENTADUETO) and alogliptin (NESINA, KAZANO, OSENI). Public Citizen’s Health Research Group petitioned the FDA in April 2012 to ban liraglutide, one of the biggest-selling drugs in these two classes, because of its link to pancreatitis, pancreatic cancer and thyroid cancer.[34]

In 2013 and 2014 respectively, the FDA approved two drugs from a new class known as SGLT2 inhibitors: canagliflozin (INVOKANA)[35] and dapagliflozin (FARXIGA).[36] We recommend that you do not use these drugs, as neither drug represents a clinical breakthrough over metformin, sulfonylureas or insulin, and both cause excretion of high levels of sugar in the urine, significantly increasing the risk of genital infections.

Oral Medications for Type 2 Diabetes

Insulin therapy

Ultimately, pills are only somewhat effective in lowering blood sugar in many patients with Type 2 diabetes, failing to adequately control blood sugar in 20 percent to 40 percent of patients.[37] This is why many patients who rely on drug treatment eventually use insulin, sometimes exclusively, to achieve control of blood sugar levels.[38]

Insulin is the most effective drug for lowering blood sugar.[39] However, like diabetes pills, insulin lowers blood sugar without treating the underlying cause of diabetes. In too large a dose, it may cause a dangerous decrease in blood sugar levels (hypoglycemia), which can cause trembling, a sensation of hunger, weakness and irritability — and in severe cases can progress to loss of consciousness.[40] Weight gain is sometimes another unfortunate side effect of insulin therapy.[41]

The ADA recommends starting insulin if blood sugar control cannot be achieved with diet and exercise plus metformin (with the option of adding a sulfonylurea prior to trying insulin).[42] Insulin is given by injection, and it requires proper education on storage and use from a doctor or diabetes nurse-educator.[43] Some people experience serious allergic reactions (skin rash, swelling, upset stomach, difficulty breathing and, very rarely, low blood pressure or even death).[44],[45]

What You Can Do

If you have been diagnosed with Type 2 diabetes, first try diet and exercise, then oral medications and finally insulin if blood sugar remains uncontrolled. (See table for a description of which oral medications to use — and not to use — before trying insulin.) Schedule regular appointments with your doctor: Diabetes is a complex disease, and your overall health and response to treatment need to be checked periodically. The frequency of appointments will depend on how well your blood sugar is controlled.

Even if you are using diet and exercise alone, you should test blood glucose at home at least once a day and share the results with your doctor.[46] Also, at least two or three times a year, your doctor should order a blood test called hemoglobin A1c or glycosylated hemoglobin.[47] This test assesses how well your blood sugar has been controlled overall during the previous two to three months and may lead your doctor to recommend changing your treatment.

Proper foot and eye care also is important for people with diabetes. This is because the disease damages blood vessels in the legs, increasing the possibility of infections and other harm. Diabetic retinopathy (eye disease) is also a major cause of blindness. Use cotton socks, wear well-fitted shoes and check your feet regularly for sores, infections and ulcers.[48] Schedule an appointment with an ophthalmologist (an eye doctor with a medical degree) at least once a year.[49]

Being diagnosed with Type 2 diabetes does not mean you are doomed to declining health. With help from your doctor and dedication to managing your symptoms, you can control this treatable disease, minimize the risk of complications and prolong your life.

References

[1] Diabetes Prevention and Treatment. Worst Pills, Best Pills. /chapters/view/11.

[2] Ibid.

[3] Ibid.

[4] Ibid.

[5] Ibid.

[6] Liu LL, Lawrence JM, Davis C, et al. Prevalence of overweight and obesity in youth with diabetes in USA: the SEARCH for Diabetes in Youth study. Pediatr Diabetes. 2010;11(1):4.

[7] Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003;289(1):76-79. http://jama.jamanetwork.com.proxy3.library.jhu.edu/article.aspx?articleid=195663.

[8] Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New England Journal of Medicine. Feb 7, 2002;346:393-403.

[9] Schellenberg ES, Dryden DM, Vandermeer B, et al. Lifestyle interventions for patients with and at risk for Type 2 Diabetes. Ann Intern Med. 2013;159(8):543-51.

[10] Ibid.

[11] American Diabetes Association. Carbohydrate Counting. http://www.diabetes.org/food-and-fitness/food/what-can-i-eat/understanding-carbohydrates/carbohydrate-counting.html.

[12] Ibid.

[13] Diabetes Prevention and Treatment. Worst Pills, Best Pills. /chapters/view/11.

[14] American Diabetes Association. Contact Us. http://www.diabetes.org/about-us/contact-us/?loc=superfooter, http://www.diabetes.org/in-my-community/local-offices/?loc=imc-slabnav

[15] Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in Type 2 Diabetes: A consensus algorithm for the initiation and adjustment of therapy. Diabetes Care. 2009;32(1):193-203.

[16] Saenz A, Fernandez-Esteban I, Mataix A, et al. Metformin monotherapy for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews. 2005;3:CD002966.

[17] UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854-865.

[18] Ibid.

[19] Ibid.

[20] Ibid.

[21] Ibid.

[22] Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in Type 2 Diabetes: A consensus algorithm for the initiation and adjustment of therapy. Diabetes Care. 2009;32(1):193-203.

[23] Ibid.

[24] Hemmingsen B, Schroll JB, Lund SS, et al. Sulphonylurea monotherapy for patients with type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2013;4: CD009008.

[25] Diabetes Prevention and Treatment. Worst Pills, Best Pills. /chapters/view/11.

[26] Hemmingsen B, Schroll JB, Lund SS, et al. Sulphonylurea monotherapy for patients with type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2013;4: CD009008.

[27] Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in Type 2 Diabetes: A consensus algorithm for the initiation and adjustment of therapy. Diabetes Care. 2009;32(1):193-203.

[28] Ibid.

[29] Drug profile: nateglinide, repaglinide. /monographs/view/47

[30] Drug profile: pioglitazone, rosiglitazone. Worst Pills, Best Pills. /monographs/view/45.

[31] Food and Drug Administration. ACTOS and AVANDIA drug labels. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021073s046lbl.pdf, http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021071s041lbl.pdf

[32] Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. NEJM. 2007;356:2457-71.

[33] Dormandy J, Charbonnel B, Eckland DJA, et al. Secondary prevention of macrovascular events in patients with type 2 928 diabetes in the PROactive study (Prospective Pioglitazone Clinical Trial in Macrovascular 929 Events): a randomized controlled trial. Lancet. 2005, 366:1279-89.

[34] Diabetes drugs linked to pancreas disease. Worst Pills, Best Pills. August 2013. /newsletters/view/864. Accessed March 7, 2014.

[35] Food and Drug Administration. Drug approval package: canagliflozin (INVOKANA) tablets. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204042Orig1s000TOC.cfm.

[36] Food and Drug Administration. Drug approval package: FARXIGA (dapagliflozin) tablets. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/202293Orig1s000TOC.cfm.

[37] Diabetes Prevention and Treatment. Worst Pills, Best Pills. /chapters/view/11.

[38] Swislocki AL, Meier JL, Najera SM, Noth RH, Long-term maintenance of glucose control in veterans with type 2 diabetes mellitus using oral agents. Metab Syndr Relat Disord. 2011;9(6):469-73.

[39] Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in Type 2 Diabetes: A consensus algorithm for the initiation and adjustment of therapy. Diabetes Care. 2009;32(1):193-203.

[40] Diabetes Prevention and Treatment. Worst Pills, Best Pills. /chapters/view/11.

[41] Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in Type 2 Diabetes: A consensus algorithm for the initiation and adjustment of therapy. Diabetes Care. 2009;32(1):193-203.

[42] Ibid.

[43] Diabetes Prevention and Treatment. Worst Pills, Best Pills. /chapters/view/11.

[44] Ibid.

[45] AMA Department of Drugs. AMA Drug Evaluations. 5th ed. Chicago: American Medical Association; 1983:1045.

[46] Diabetes Prevention and Treatment. Worst Pills, Best Pills. /chapters/view/11.

[47] Ibid.

[48] Ibid.

[49] Ibid.