The thiazolidinedione Rosiglitazone ( Avandia ) is an insulin sensitizer that is indicated for use either as monotherapy or in combination with Metformin or a sulfonylurea in patients whose type 2 diabetes is inadequately controlled by diet and exercise alone.

In the January 2006 issue of the Canadian Adverse Reaction Newsletter, it was reported that Health Canada had received 5 domestic reports of parotid gland enlargement suspected of being associated with the use of Rosiglitazone.
As of Dec. 31, 2006, 1 additional domestic report was received.
All 6 cases involved patients who experienced visibly evident enlargement of one or both parotid glands while taking the drug. In 4 cases the adverse reaction was alleviated or resolved when the Rosiglitazone therapy was stopped; in the remaining 2 cases this information was not provided.

The parotid glands are the largest of the salivary glands and are located in the facial subcutaneous tissue, over the posterior aspect of each mandibular ramus. There is considerable variation in the size of parotid glands of healthy individuals, but on clinical examination they are not visible and are not readily palpable.
Nontender parotid gland enlargement has been associated with a number of medical disorders ( e.g., diabetes mellitus, obesity and hyperlipidemia ) and medications ( e.g., iodides, Phenylbutazone and Propylthiouracil ).

Rosiglitazone is a highly selective and potent agonist for the peroxisome proliferator-activated receptor gamma ( PPAR-gamma ).
Although Rosiglitazone appears to be associated with some effects that are not mediated by PPAR-gamma, binding of Rosiglitazone to PPAR-gamma seems to be an important component of its mechanism of action.
In addition, PPAR-gamma-responsive genes participate in the regulation of fatty acid metabolism and in the maturation of preadipocytes, predominantly of subcutaneous origin.
Although PPAR-gamma is also implicated in various functions in the parotid glands,9, 10, 11 the activity of Rosiglitazone in the parotid glands is not fully understood. Further studies are required to confirm whether the drug causes noticeable parotid gland enlargement by acting directly on the parotid tissue through its agonist activity on PPAR-gamma, or indirectly through induction of weight gain or elevation of serum lipid levels, or by another mechanism.

Parotid gland enlargement may be due to diabetes alone and may become clinically evident during treatment with Rosiglitazone. When a diabetic patient taking Rosiglitazone experiences nontender parotid gland enlargement, the drug may be considered as a possible cause.

Source: Health Canada, 2007

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