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PubMed Clinical Q&A [Internet].

Comparing newer drugs for diabetes, including combination drugs

Laura Dean, MD.

Created: May 16, 2011.

More than 20 million Americans have diabetes. Type 1 diabetes is treated with insulin whereas a variety of oral medications may be used to lower blood sugar levels in people with type 2 diabetes. About 70% of people with type 2 diabetes will eventually require more than one type of oral medication, with or without insulin.

Thiazolidiones (TZDs) are one type of oral medication, which may be given as monotherapy (single medication), given with other medications separately, or in some cases given as a combination drug, containing a fixed dose of thiazolidione plus a fixed dose of another type of drug.

Recently, several newer diabetes medications have been approved which target different receptors and hormones than those of "traditional" oral agents. Exenatide, liraglutide, saxagliptin, sitagliptin, and pramlintide have been approved to treat type 2 diabetes, and pramlintide has also been approved as an add-on therapy to insulin to treat type 1 diabetes.

The "Drug Class Review on Newer Diabetes Medications, TZDs, and Combinations" compares the safety and effectiveness of 12 drugs. A summary of the findings is below.

How do newer drugs for diabetes compare in lowering blood sugar levels?

In adults with type 2 diabetes, all the newer diabetes drugs (exenatide, liraglutide, pramlintide, saxagliptin, and sitagliptin) lower HbA1c compared to placebo.

Overall, the strength of evidence is low to moderate, depending on the comparison. In terms of lowering HbA1c:

How do newer drugs for diabetes compare in safety?

In adults with type 2 diabetes, exenatide appears to share similar rates of hypoglycemia with insulin. The rates of hypoglycemia tended to be lower with liraglutide (when compared to glimepiride or exenatide) and lower with sitagliptin (when compared to glipizide). Evidence suggests that sitagliptin and saxagliptin share similar hypoglycemia rates with placebo.

None of the newer drugs appear to cause weight gain. In the short term (up to 6 months), pramlintide, exenatide, and liraglutide appear to cause weight loss, whereas sitagliptin and saxagliptin are likely weight neutral. [full review]

How do thiazolidinediones compare in lowering blood sugar levels?

In patients with type 2 diabetes, both pioglitazone and rosiglitazone reduce HbA1c by about 1%, which is a similar change produced by other oral drugs such as metformin, and the sulfonylureas. [full review]

How do thiazolidinediones compare in safety?

The risk of hypoglycemia is lower with thiazolidinediones compared to sulfonylureas, but similar to the risk with metformin.

In terms of weight gain, both pioglitazone and rosiglitazone cause a similar amount of weight gain to that caused by sulfonylureas.

Pioglitazone and rosiglitazone both increase the risk of heart failure, edema, and fractures in women. There is no evidence that pioglitazone increases the risk of death from a cardiovascular cause, or any cause; rosiglitazone now has restricted access due to an increased risk of cardiovascular adverse events. [full review]

How do combination drugs compare in lowering blood sugar?

The following drugs lowered HbA1c more than monotherapy with any of their respective component drugs: Avandamet, Avandaryl, Actoplus Met, and dual therapy with metformin and sitagliptin. [full review]

Drugs included in this review

Generic nameDrug ClassTrade namesForm
PramlintideAmylin agonistSymlinInjection
SitagliptinDPP-4 InhibitorJanuviaTablet
SaxagliptinDPP-4 InhibitorOnglyzaTablet
ExenatideGLP-1 Agonists
(Incretin mimetics)
LiraglutideGLP-1 Agonists
(Incretin mimetics)

Abbreviations: DPP-4, Dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1

Combination drugs included in this review

Generic NameTrade Names
Rosiglitazone + MetforminAvandamet
Pioglitazone + MetforminActoplus Met
Actoplus Met XR
Rosiglitazone + GlimepirideAvandaryl
Pioglitazone + GlimepirideDuetact
Sitagliptin + MetforminJanumet

Further Information

Image th-tzdcombin11.jpgThis PubMed Clinical Q&A was reviewed by Dan Jonas, MD, MPH.

For the full report and evidence tables, please see:
Jonas D, Van Scoyoc E, Gerrald K, Wines R, Amick H, Runge T, Triplette M. Drug Class Review on Newer Diabetes Medications, TZDs, and Combinations [Internet]. Portland (OR): Oregon Health & Science University; 2011 Feb. Available at http://www.ncbi.nlm.nih.gov/books/NBK54209/.


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