Sitagliptin: Difference between revisions

Line 106:

Common side effects include headaches, swelling of the legs, and [[upper respiratory tract infections]].~~<ref name=AHFS2019/>~~ Serious side effects may include [[angioedema]], [[low blood sugar]], [[kidney problems]], [[pancreatitis]], and [[joint pain]]. Whether use in [[pregnancy]] or [[breastfeeding]] is safe is unclear. It is in the [[DPP-4 inhibitors|dipeptidyl peptidase-4 (DPP-4) inhibitor]] class and works by increasing the production of [[insulin]] and decreasing the production of [[glucagon]] by the pancreas.

Common side effects include headaches, swelling of the legs, and [[upper respiratory tract infections]]. Serious side effects may include [[angioedema]], [[low blood sugar]], [[kidney problems]], [[pancreatitis]], and [[joint pain]]. Whether use in [[pregnancy]] or [[breastfeeding]] is safe is unclear. It is in the [[DPP-4 inhibitors|dipeptidyl peptidase-4 (DPP-4) inhibitor]] class and works by increasing the production of [[insulin]] and decreasing the production of [[glucagon]] by the pancreas.

Sitagliptin was developed by [[Merck & Co.]] and approved for medical use in the United States in 2006.~~<ref name=AHFS2019/>~~ In 2021, it was the 83rd most commonly prescribed medication in the United States, with more than 8{{nbsp}}million prescriptions. It is available as a [[generic medication]] in Canada but not the United States.

Sitagliptin was developed by [[Merck & Co.]] and approved for medical use in the United States in 2006. In 2021, it was the 83rd most commonly prescribed medication in the United States, with more than 8{{nbsp}}million prescriptions. It is available as a [[generic medication]] in Canada but not the United States.

==Medical uses==

Line 121:

The existence of rare case reports of [[kidney failure]] and hypersensitivity reactions is noted in the United States prescribing information, but a causative role for sitagliptin has not been established.

Several [[postmarketing surveillance|postmarketing reports]] of [[pancreatitis]] (some fatal) have been made in people treated with sitagliptin and other DPP-4 inhibitors, and the U.S. package insert carries a warning to this effect,~~<ref name="Januvia FDA label" />~~ although the causal link between sitagliptin and pancreatitis has not yet been fully substantiated. One study with lab rats published in 2009 concluded that some of the possible risks of pancreatitis or pancreatic cancer may be reduced when it is used with metformin. However, while DPP-4 inhibitors showed an increase in such risk factors, as of 2009, no increase in pancreatic cancer has been reported in individuals taking DPP-4 inhibitors.

Several [[postmarketing surveillance|postmarketing reports]] of [[pancreatitis]] (some fatal) have been made in people treated with sitagliptin and other DPP-4 inhibitors, and the U.S. package insert carries a warning to this effect, although the causal link between sitagliptin and pancreatitis has not yet been fully substantiated. One study with lab rats published in 2009 concluded that some of the possible risks of pancreatitis or pancreatic cancer may be reduced when it is used with metformin. However, while DPP-4 inhibitors showed an increase in such risk factors, as of 2009, no increase in pancreatic cancer has been reported in individuals taking DPP-4 inhibitors.

In 2015, the U.S. Food and Drug Administration (FDA) added a new warning and precaution about the risk of "severe and disabling" joint pain to the labels of all DPP-4 inhibitor medicines.

Line 128:

Sitagliptin works to [[competitive inhibition|competitively inhibit]] the [[enzyme]] dipeptidyl peptidase 4 (DPP-4). This enzyme breaks down the [[incretin]]s [[GLP-1]] and GIP, [[gastrointestinal hormone]]s released in response to a meal. By preventing breakdown of GLP-1 and GIP, they are able to increase the secretion of insulin and suppress the release of glucagon by the alpha cells of the pancreas.~~{{medcn|date=May 2022}}~~ This drives blood glucose levels towards normal.~~{{medcn|date=May 2022}}~~ As the blood glucose level approaches normal, the amounts of insulin released and glucagon suppressed diminishes, thus tending to prevent an "overshoot" and subsequent low blood sugar (hypoglycemia), which is seen with some other oral hypoglycemic agents.

Sitagliptin works to [[competitive inhibition|competitively inhibit]] the [[enzyme]] dipeptidyl peptidase 4 (DPP-4). This enzyme breaks down the [[incretin]]s [[GLP-1]] and GIP, [[gastrointestinal hormone]]s released in response to a meal. By preventing breakdown of GLP-1 and GIP, they are able to increase the secretion of insulin and suppress the release of glucagon by the alpha cells of the pancreas. This drives blood glucose levels towards normal. As the blood glucose level approaches normal, the amounts of insulin released and glucagon suppressed diminishes, thus tending to prevent an "overshoot" and subsequent low blood sugar (hypoglycemia), which is seen with some other oral hypoglycemic agents.

Sitagliptin has been shown to lower [[HbA1c]] level by about 0.7% points versus placebo. It is slightly less effective than metformin when used as a [[monotherapy]]. It does not cause weight gain and has less hypoglycemia compared to sulfonylureas. Sitagliptin is recommended as a second-line drug (in combination with other drugs) after the combination of diet/exercise and metformin fails.

@@ Line 106: / Line 106: @@
 <!-- Side effects and mechanisms -->
-Common side effects include headaches, swelling of the legs, and [[upper respiratory tract infections]].<ref name=AHFS2019/> Serious side effects may include [[angioedema]], [[low blood sugar]], [[kidney problems]], [[pancreatitis]], and [[joint pain]]. Whether use in [[pregnancy]] or [[breastfeeding]] is safe is unclear. It is in the [[DPP-4 inhibitors|dipeptidyl peptidase-4 (DPP-4) inhibitor]] class and works by increasing the production of [[insulin]] and decreasing the production of [[glucagon]] by the pancreas.
+Common side effects include headaches, swelling of the legs, and [[upper respiratory tract infections]]. Serious side effects may include [[angioedema]], [[low blood sugar]], [[kidney problems]], [[pancreatitis]], and [[joint pain]]. Whether use in [[pregnancy]] or [[breastfeeding]] is safe is unclear. It is in the [[DPP-4 inhibitors|dipeptidyl peptidase-4 (DPP-4) inhibitor]] class and works by increasing the production of [[insulin]] and decreasing the production of [[glucagon]] by the pancreas.
 <!-- Society and culture -->
-Sitagliptin was developed by [[Merck & Co.]] and approved for medical use in the United States in 2006.<ref name=AHFS2019/> In 2021, it was the 83rd most commonly prescribed medication in the United States, with more than 8{{nbsp}}million prescriptions. It is available as a [[generic medication]] in Canada but not the United States.
+Sitagliptin was developed by [[Merck & Co.]] and approved for medical use in the United States in 2006. In 2021, it was the 83rd most commonly prescribed medication in the United States, with more than 8{{nbsp}}million prescriptions. It is available as a [[generic medication]] in Canada but not the United States.
 ==Medical uses==
@@ Line 121: / Line 121: @@
 The existence of rare case reports of [[kidney failure]] and hypersensitivity reactions is noted in the United States prescribing information, but a causative role for sitagliptin has not been established.
-Several [[postmarketing surveillance|postmarketing reports]] of [[pancreatitis]] (some fatal) have been made in people treated with sitagliptin and other DPP-4 inhibitors, and the U.S. package insert carries a warning to this effect,<ref name="Januvia FDA label" /> although the causal link between sitagliptin and pancreatitis has not yet been fully substantiated. One study with lab rats published in 2009 concluded that some of the possible risks of pancreatitis or pancreatic cancer may be reduced when it is used with metformin. However, while DPP-4 inhibitors showed an increase in such risk factors, as of 2009, no increase in pancreatic cancer has been reported in individuals taking DPP-4 inhibitors.
+Several [[postmarketing surveillance|postmarketing reports]] of [[pancreatitis]] (some fatal) have been made in people treated with sitagliptin and other DPP-4 inhibitors, and the U.S. package insert carries a warning to this effect, although the causal link between sitagliptin and pancreatitis has not yet been fully substantiated. One study with lab rats published in 2009 concluded that some of the possible risks of pancreatitis or pancreatic cancer may be reduced when it is used with metformin. However, while DPP-4 inhibitors showed an increase in such risk factors, as of 2009, no increase in pancreatic cancer has been reported in individuals taking DPP-4 inhibitors.
 In 2015, the U.S. Food and Drug Administration (FDA) added a new warning and precaution about the risk of "severe and disabling" joint pain to the labels of all DPP-4 inhibitor medicines.
@@ Line 128: / Line 128: @@
 {{see also|Dipeptidyl peptidase-4 inhibitors}}
-Sitagliptin works to [[competitive inhibition|competitively inhibit]] the [[enzyme]] dipeptidyl peptidase 4 (DPP-4). This enzyme breaks down the [[incretin]]s [[GLP-1]] and GIP, [[gastrointestinal hormone]]s released in response to a meal. By preventing breakdown of GLP-1 and GIP, they are able to increase the secretion of insulin and suppress the release of glucagon by the alpha cells of the pancreas.{{medcn|date=May 2022}} This drives blood glucose levels towards normal.{{medcn|date=May 2022}} As the blood glucose level approaches normal, the amounts of insulin released and glucagon suppressed diminishes, thus tending to prevent an "overshoot" and subsequent low blood sugar (hypoglycemia), which is seen with some other oral hypoglycemic agents.
+Sitagliptin works to [[competitive inhibition|competitively inhibit]] the [[enzyme]] dipeptidyl peptidase 4 (DPP-4). This enzyme breaks down the [[incretin]]s [[GLP-1]] and GIP, [[gastrointestinal hormone]]s released in response to a meal. By preventing breakdown of GLP-1 and GIP, they are able to increase the secretion of insulin and suppress the release of glucagon by the alpha cells of the pancreas. This drives blood glucose levels towards normal. As the blood glucose level approaches normal, the amounts of insulin released and glucagon suppressed diminishes, thus tending to prevent an "overshoot" and subsequent low blood sugar (hypoglycemia), which is seen with some other oral hypoglycemic agents.
 Sitagliptin has been shown to lower [[HbA1c]] level by about 0.7% points versus placebo. It is slightly less effective than metformin when used as a [[monotherapy]]. It does not cause weight gain and has less hypoglycemia compared to sulfonylureas. Sitagliptin is recommended as a second-line drug (in combination with other drugs) after the combination of diet/exercise and metformin fails.