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There has been talk in the past of why not suppress glucagon instead of using insulin well it's not that simple;
Complete article here;
Clinical Trials, Triumphs, and Tribulations of Glucagon Receptor Antagonists - Diabetes Care 2016
http://care.diabetesjournals.org/content/39/7/1075.full
Another concern of GRA therapy would be the development of glycogen storage disease. In mice, a fourfold increase of glycogen has been reported in glucagon receptor–null mice (22). With LY2409021, changes were not seen in rodents but were noted in cynomolgus monkeys (23). This will be important to investigate, as it may offer a potential explanation for the elevated ALT levels. Notably, most glycogen storage diseases present with elevated ALT and aspartate aminotransferase (AST). Glycogen content in human subjects has not been reported yet with this candidate drug.
Increased liver enzymes are perhaps the most commonly observed side effect of GRA treatment. Three of the 85 patients in the study by Kazda et al. (1) showed ALT levels more than three times the upper limit of normal. AST also increased, albeit to a lesser degree. In the phase 2b study, 8 of the 191 patients showed increases in ALT, which exceeded three times the upper limit of normal. The U.S. Food and Drug Administration guidelines for drug-induced liver injury are defined by a threefold ALT/AST increase, with concurrent increases in alkaline phosphatase by twofold and total bilirubin by twofold. None of the subjects with high ALT levels showed concomitant increases in bilirubin, alkaline phosphatase, or symptoms of liver disease. It is possible that increased glycogen content may account for some changes in liver enzymes. Alternatively, this may be driven by an alternative means of handling the amino acids, which would otherwise be used for gluconeogenesis. Regardless, the small degree of change in AST/ALT, in the absence of other markers of liver toxicity (alkaline phosphatase or bilirubin), suggests that these drugs would not exceed U.S. Food and Drug Administration guidelines for drug-induced liver injury.
The most severe concern with GRA therapy is malignant transformation of α-cells, as they undergo marked hyperplasia when the action of their secretory product is blocked. As glucagon promotes depletion of amino acids by stimulating their use as gluconeogenic substrates (24), GRAs promote an increase in hepatic and circulating amino acids. In turn, this can lead to enhanced α-cell proliferation by enhancing mechanistic target of rapamycin activation within the α-cell (25). Although we have yet to encounter a glucagonoma in any of the animals treated chronically with glucagon receptor antibodies, the disease (glucagonoma) is such a terrible one that one may consider monitoring patients treated with GRAs. A very early marker of glucagonoma is easily detectable by monitoring a COOH-terminal extension of the glucagon molecule.
There has been talk in the past of why not suppress glucagon instead of using insulin well it's not that simple;
Complete article here;
Clinical Trials, Triumphs, and Tribulations of Glucagon Receptor Antagonists - Diabetes Care 2016
http://care.diabetesjournals.org/content/39/7/1075.full
Another concern of GRA therapy would be the development of glycogen storage disease. In mice, a fourfold increase of glycogen has been reported in glucagon receptor–null mice (22). With LY2409021, changes were not seen in rodents but were noted in cynomolgus monkeys (23). This will be important to investigate, as it may offer a potential explanation for the elevated ALT levels. Notably, most glycogen storage diseases present with elevated ALT and aspartate aminotransferase (AST). Glycogen content in human subjects has not been reported yet with this candidate drug.
Increased liver enzymes are perhaps the most commonly observed side effect of GRA treatment. Three of the 85 patients in the study by Kazda et al. (1) showed ALT levels more than three times the upper limit of normal. AST also increased, albeit to a lesser degree. In the phase 2b study, 8 of the 191 patients showed increases in ALT, which exceeded three times the upper limit of normal. The U.S. Food and Drug Administration guidelines for drug-induced liver injury are defined by a threefold ALT/AST increase, with concurrent increases in alkaline phosphatase by twofold and total bilirubin by twofold. None of the subjects with high ALT levels showed concomitant increases in bilirubin, alkaline phosphatase, or symptoms of liver disease. It is possible that increased glycogen content may account for some changes in liver enzymes. Alternatively, this may be driven by an alternative means of handling the amino acids, which would otherwise be used for gluconeogenesis. Regardless, the small degree of change in AST/ALT, in the absence of other markers of liver toxicity (alkaline phosphatase or bilirubin), suggests that these drugs would not exceed U.S. Food and Drug Administration guidelines for drug-induced liver injury.
The most severe concern with GRA therapy is malignant transformation of α-cells, as they undergo marked hyperplasia when the action of their secretory product is blocked. As glucagon promotes depletion of amino acids by stimulating their use as gluconeogenic substrates (24), GRAs promote an increase in hepatic and circulating amino acids. In turn, this can lead to enhanced α-cell proliferation by enhancing mechanistic target of rapamycin activation within the α-cell (25). Although we have yet to encounter a glucagonoma in any of the animals treated chronically with glucagon receptor antibodies, the disease (glucagonoma) is such a terrible one that one may consider monitoring patients treated with GRAs. A very early marker of glucagonoma is easily detectable by monitoring a COOH-terminal extension of the glucagon molecule.
